Biorefining compounds and organocatalytic upgrading methods

ABSTRACT

The invention provides new methods for the direct umpolung self-condensation of 5-hydroxymethylfurfural (HMF) by organocatalysis, thereby upgrading the readily available substrate into 5,5′-di(hydroxymethyl) furoin (DHMF). While many efficient catalyst systems have been developed for conversion of plant biomass resources into HMF, the invention now provides methods to convert such nonfood biomass directly into DHMF by a simple process as described herein. The invention also provides highly effective new methods for upgrading other biomass furaldehydes and related compound to liquid fuels. The methods include the organocatalytic self-condensation (umpolung) of biomass furaldehydes into (C 8 -C 12 )furoin intermediates, followed by hydrogenation, etherification or esterification into oxygenated biodiesel, or hydrodeoxygenation by metal-acid tandem catalysis into premium hydrocarbon fuels.

RELATED APPLICATIONS

This application is a divisional application of U.S. patent applicationSer. No. 13/934,074, filed Jul. 2, 2013, which claims priority under 35U.S.C. §119(e) to U.S. Provisional Patent Application No. 61/667,693filed Jul. 3, 2012, 61/698,171 filed Sep. 7, 2012, and 61/817,162 filedApr. 29, 2013, which applications are incorporated herein by reference.

GOVERNMENT SUPPORT

This invention was made with government support under Grant No.DE-FG02-10ER16193 awarded by the Department of Energy. The governmenthas certain rights in the invention.

BACKGROUND OF THE INVENTION

Owing to their unique ability to dissolve lignocellulosic biomass andrelated carbohydrates under relatively mild conditions, plus severalother concurrent advantages (e.g., as designable and recyclable solventswith low volatility and toxicity), ionic liquids (ILs) such as1-alkyl(R)-3-methyl(M)imidazolium(IM) chloride salts, [RMIM]Cl, haveattracted rapidly growing interest, particularly in the pursuit ofrenewable energy and sustainable chemicals from plant biomass. Forinstance, ILs have enabled homogenous hydrolysis of cellulose to sugarsin high to quantitative conversion, in the presence or absence ofcatalyst, and catalyzed conversion of glucose or cellulose into thebiomass platform chemical 5-hydroxymethylfurfural (HMF), a key andversatile biorefining intermediate for value-added chemicals and liquidfuels. Upgrading of HMF can be achieved by metal-catalyzedtransformations such as hydrogenation/hydrogenolysis into2,5-dimethylfuran, a liquid fuel with a 40% higher energy density thanethanol, and aldol condensation with organic compounds followed bydehydration/hydrogenation into C₉ to C₁₅ liquid alkanes (fuels), thusupgrading it into the kerosene/jet fuel range (C₈ to C₁₆). Directcoupling of two HMF molecules would make a C₁₂ biofuel intermediate, butHMF or furfural cannot undergo aldol self-condensation because theypossess no α-H.

Accordingly, new methods are needed for upgrading HMF into usefulintermediates and products. New methods for coupling HMF would providesuch valuable intermediates for use as products such as chemicals forsynthetic chemistry and liquids for jet or diesel fuels and the like.

SUMMARY

The invention also provides highly effective new methods for upgradingbiomass furaldehydes and related compound to useful chemicalintermediates and liquid fuels. The methods include the organocatalyticumpolung self-condensation of biomass furaldehydes into (C₁₀-C₁₂)furoinintermediates, followed by reactions such as hydrogenation,etherification or esterification, to provide oxygenated biodiesel, orhydrodeoxygenation by metal-acid tandem catalysis to provide premiumhydrocarbon fuels.

For example, the invention also provides new methods for the directumpolung self-condensation of 5-hydroxymethylfurfural (HMF) byorganocatalysis, thereby upgrading the readily available substrate into5,5′-di(hydroxymethyl) furoin (DHMF). While many efficient catalystsystems have been developed for conversion of plant biomass resourcesinto HMF, the invention now provides methods to convert such nonfoodbiomass directly into DHMF and modified compounds thereof by simpleprocesses as described herein.

Accordingly, the invention provides new compounds and methods asdescribed below. In one embodiment, the invention provides a compound ofFormula I:

wherein each R¹ is independently H, OH, halo, amine, alkylamino,dialkylamino, alkoxy, or acyloxy; and R² is OH, halo, amine, alkylamino,dialkylamino, alkoxy, or acyloxy. In some embodiments, at least one R¹is not H. In some embodiments, R² can be oxidized to provide a carbonyl,thereby providing the corresponding 1,2-diketone compound. In certainembodiments, the carbonyl of Formula (I) can be reduced to provide ahydroxyl, or a compound having an independently selected R² in place ofthe carbonyl oxygen.

In another embodiment, the invention provides a compound of Formula II:

wherein R¹ is H, OH, halo, amine, alkylamino, dialkylamino, alkoxy, oracyloxy; and R² is H, OH, halo, amine, alkylamino, dialkylamino, alkoxy,or acyloxy. The invention also provides compositions that include one ormore compounds of Formula (I) or (II) and one or more (C₁₀-C₂₂)alkanes.

The invention also provides an organocatalytic method to couple afuraldehyde compound, such as a compound of Formula (X), and a secondfuraldehyde compound. The method can include contacting a firstfuraldehyde compound and a second furaldehyde compound in the presenceof an ionic liquid under conditions where the ionic liquid forms anN-heterocyclic carbene (NHC), or by contacting the furaldehydes in thepresence of a discrete NHC, to provide a coupled product, such as acompound that includes a (C₁₀-C₁₂)furoin moiety. In some embodiments,the product will include a substituent at a furan 5-position, such ashydroxymethyl. In other embodiments, the product can includesubstituents at both the 5-position and the 5′-positions of the coupledfuran products. The furans can be substituted on the furan ring at the3, 4, 3′, or 4′ positions. The hydroxy group of a hydroxymethyl group atthe 5-position and/or the 5′-position can further be modified, asdescribed below.

In another embodiment, the invention provides an organocatalytic methodto homocouple 5-hydroxymethylfurfural (HMF) comprising contacting HMFand an ionic liquid under conditions wherein the ionic liquid forms anN-heterocyclic carbene (NHC), or by contacting HMF and a discrete NHC,to provide 5,5′-di(hydroxymethyl)furoin (DHMF).

In yet another embodiment, the invention provides methods to prepare(C₈-C₂₂)alkanes. The methods can include contacting a compound ofFormula I:

wherein R¹ and R² can be as described above for Formula (I); orcontacting a compound of Formula II:

wherein R¹ and R² can be as described above for Formula (II); with abifunctional catalyst systems that comprises a noble metal, such aspalladium or platinum metal, and an acidic moiety under reactionconditions comprising heat and H₂ pressure in water; thereby reducingthe compound of Formula (I) or (II) to provide one or more(C₈-C₂₂)alkanes. The acidic moiety can be, for example, a liquid orsolid acid. In some embodiments, at least one R¹ of Formula (I) orFormula (II) is not H.

The invention thus provides novel compounds of the formulas describedherein, intermediates for their synthesis, methods of preparing thecompounds described herein, and useful downstream products of thecompounds such as fuels and chemical intermediates.

BRIEF DESCRIPTION OF THE DRAWINGS

The following drawings form part of the specification and are includedto further demonstrate certain embodiments or various aspects of theinvention. In some instances, embodiments of the invention can be bestunderstood by referring to the accompanying drawings in combination withthe detailed description presented herein. The description andaccompanying drawings may highlight a certain specific example, or acertain aspect of the invention. However, one skilled in the art willunderstand that portions of the example or aspect may be used incombination with other examples or aspects of the invention.

FIG. 1. Formation of a new compound (DHMF) as detected by HPLC from theHMF degradation reaction mixture in [EMIM]OAc at 80° C.: a) crudesample; b) after purification by silica gel column chromatography.

FIG. 2. X-ray crystal structure of 5,5′-di(hydroxymethyl)furoin (DHMF)showing two independent molecules associated with each by moderatehydrogen bonds with minor structural differences in the unit cell.Hydrogen atoms have been omitted for clarity and ellipsoids drawn at 50%probability.

FIG. 3A. Proposed catalytic cycle for umpolung self-condensation of HMFto DHMF by a catalytic IL, [EMIM]OAc.

FIG. 3B. A schematic representation of the conversion of HMF to DHMF byan N-heterocyclic carbene (NHC).

FIG. 4. ¹H NMR spectrum of the reaction between HMF and [EMIM]OAc (1:5molar ratio) at RT for 1.5 hours, showing clean formation ofintermediate II in the presence of excess [EMIM]OAc (small unlabeledpeaks are for a trace amount of the residual solvents brought from theIL).

FIG. 5. ¹³C NMR spectrum of the reaction between HMF and [EMIM]OAc (in a1:5 molar ratio) at RT for 1.5 hours, showing clean formation ofintermediate II in the presence of excess [EMIM]OAc (a peak unlabeled isfor a trace amount of the residual solvent (CH₂Cl₂) brought from theIL).

FIG. 6. Comparison of ¹H NMR spectra of the reaction between HMF and[EMIM]OAc (1:1 molar ratio) in DMSO-d₆ at 80° C. over the initial 25minute period. This spectral overlay in the most characteristic regionshows the gradual decreasing of the intensities (normalized by the C₆Me₆internal standard) of the peaks for HMF (6.59 ppm, “A” line) andintermediate II (6.73, 6.39, 6.26 ppm, “B” lines), with the concomitantincreasing of DHMF (6.48, 6.29, 6.19, 5.72 ppm, “C” lines). A smallshoulder peak at 5.74 with a constant intensity is the residual solvent(CH₂Cl₂) brought from the IL.

FIG. 7. Graphical profiles of HMF degradation (mol %) in [EMIM]OAc (1:1molar ratio) vs. time at two different temperatures (50° C. and 80° C.),monitored by HPLC.

FIG. 8. Profile (by NMR) of HMF degradation in [EMIM]OAc (1:1 molarratio) at 80° C., showing rapid HMF degradation by 17.1% at 0 min, 47.1%at 2 min, 56.8% at 5 min, 74.2% at 10 min, 81.9% at 15 min, 84.0% at 20min, 86.1% at 25 min, 88.5 at 45 min, and 89.6% at 60 min.

FIG. 9. The first-order plot of the HMF degradation in [EMIM]OAc (1:1molar ratio) at 80° C. for the initial time period (2-15 minutes).

FIG. 10. ¹H and ¹³C NMR spectra of DHMF in methanol-d₄. Note that peaksat 3.31 ppm and 4.87 ppm on the ¹H NMR spectrum are for the NMR solventresidual and H₂O signals, respectively. The methanol residual signal at49.86 ppm on the ¹³C NMR spectrum is not shown in the expansion regionof the spectrum illustrated in the figure.

FIG. 11. DHMF yield (by NMR) as a function of HMF degradation time in[EMIM]OAc (1:1 molar ratio) at 80° C.

FIG. 12. ¹H NMR (DMSO-d₆) of DHMF derived from umpolung condensation ofHMF by TPT. Note the three broad peaks centered at ˜5.3 ppm, 5.5 ppm,and 6.1 ppm, not appeared in the ¹H NMR taken in methanol-d₄ (FIG. 10),are for three types of the OH groups present in DHMF, and the peak at2.54 ppm is from the residual solvent signal.

FIG. 13. ¹H NMR spectrum of the resulting enaminol (the Breslowintermediate) derived from the reaction of HMF and IMes.

FIG. 14. GC-MS chromatogram of the organic phase products produced byHDO of DHMF catalyzed by Pt/CsH₂PW₁₂O₄₀.

FIG. 15. GC-MS chromatogram of the organic phase products produced byHDO of DHMF catalyzed by Pt/C+TaOPO₄.

DETAILED DESCRIPTION

The invention provides new compounds and methods for preparing liquidalkanes and derivatives thereof in a targeted range from C₁₀ to aboutC₂₂. The compounds can be produced from biomass-derived carbohydratessuch as 5-hydroxymethylfurfural (HMF), 5,5′-di(hydroxymethyl)furoin(DHMF), furoin, and similar furan compounds. The invention not onlyprovides a route for using renewable biomass resources to diminish thereliance on petroleum-based liquid fuels, but it also provides a fuelwith a specific range of carbon-atom chain lengths without the use ofrefining techniques. This latter feature makes the methods describedherein especially attractive for producing alkane mixtures havingdefined characteristics, such as jet fuel, where specific physicalproperties are required (e.g., high energy density with narrow molecularweight distribution), that are unattainable with current biofuels. Thus,the invention provides catalytic processes for converting carbohydratesin general, and biomass-derived carbohydrates and byproducts inparticular, to liquid, long-chain alkanes in the higher mass ranges(i.e., about C₁₀-C₂₂) that can be used, for example, as sulfur-free fuelcomponents and as other valuable chemicals and intermediates.

Definitions

As used herein, the recited terms have the following meanings. All otherterms and phrases used in this specification have their ordinarymeanings as one of skill in the art would understand. Such ordinarymeanings may be obtained by reference to technical dictionaries, such asHawley's Condensed Chemical Dictionary 14th Edition, by R. J. Lewis,John Wiley & Sons, New York, N.Y., 2001.

References in the specification to “one embodiment”, “an embodiment”,etc., indicate that the embodiment described may include a particularaspect, feature, structure, moiety, or characteristic, but not everyembodiment necessarily includes that aspect, feature, structure, moiety,or characteristic. Moreover, such phrases may, but do not necessarily,refer to the same embodiment referred to in other portions of thespecification. Further, when a particular aspect, feature, structure,moiety, or characteristic is described in connection with an embodiment,it is within the knowledge of one skilled in the art to affect orconnect such aspect, feature, structure, moiety, or characteristic withother embodiments, whether or not explicitly described.

The singular forms “a,” “an,” and “the” include plural reference unlessthe context clearly dictates otherwise. Thus, for example, a referenceto “a compound” includes a plurality of such compounds, so that acompound X includes a plurality of compounds X. It is further noted thatthe claims may be drafted to exclude any optional element. As such, thisstatement is intended to serve as antecedent basis for the use ofexclusive terminology, such as “solely,” “only,” and the like, inconnection with any element described herein, and/or the recitation ofclaim elements or use of “negative” limitations.

The term “and/or” means any one of the items, any combination of theitems, or all of the items with which this term is associated. Thephrase “one or more” is readily understood by one of skill in the art,particularly when read in context of its usage. For example, one or moresubstituents on a furan ring refers to one to four, one to three, or oneto two, for example if the furan ring is disubstituted.

The term “about” can refer to a variation of ±5%, ±10%, ±20%, or ±25% ofthe value specified. For example, “about 50” percent can in someembodiments carry a variation from 45 to 55 percent. For integer ranges,the term “about” can include one or two integers greater than and/orless than a recited integer at each end of the range. Unless indicatedotherwise herein, the term “about” is intended to include values, e.g.,weight percentages, proximate to the recited range that are equivalentin terms of the functionality of the individual ingredient, thecomposition, or the embodiment. The term about can also modify theend-points of a recited range as discuss above in this paragraph.

As will be understood by the skilled artisan, all numbers, includingthose expressing quantities of ingredients, properties such as molecularweight, reaction conditions, and so forth, are approximations and areunderstood as being optionally modified in all instances by the term“about.” These values can vary depending upon the desired propertiessought to be obtained by those skilled in the art utilizing theteachings of the descriptions herein. It is also understood that suchvalues inherently contain variability necessarily resulting from thestandard deviations found in their respective testing measurements.

As will be understood by one skilled in the art, for any and allpurposes, particularly in terms of providing a written description, allranges recited herein also encompass any and all possible sub-ranges andcombinations of sub-ranges thereof, as well as the individual valuesmaking up the range, particularly integer values. A recited range (e.g.,weight percentages or carbon groups) includes each specific value,integer, decimal, or identity within the range. Any listed range can beeasily recognized as sufficiently describing and enabling the same rangebeing broken down into at least equal halves, thirds, quarters, fifths,or tenths. As a non-limiting example, each range discussed herein can bereadily broken down into a lower third, middle third and upper third,etc. As will also be understood by one skilled in the art, all languagesuch as “up to”, “at least”, “greater than”, “less than”, “more than”,“or more”, and the like, include the number recited and such terms referto ranges that can be subsequently broken down into sub-ranges asdiscussed above. In the same manner, all ratios recited herein alsoinclude all sub-ratios falling within the broader ratio. Accordingly,specific values recited for radicals, substituents, and ranges, are forillustration only; they do not exclude other defined values or othervalues within defined ranges for radicals and substituents.

One skilled in the art will also readily recognize that where membersare grouped together in a common manner, such as in a Markush group, theinvention encompasses not only the entire group listed as a whole, buteach member of the group individually and all possible subgroups of themain group. Additionally, for all purposes, the invention encompassesnot only the main group, but also the main group absent one or more ofthe group members. The invention therefore envisages the explicitexclusion of any one or more of members of a recited group. Accordingly,provisos may apply to any of the disclosed categories or embodimentswhereby any one or more of the recited elements, species, orembodiments, may be excluded from such categories or embodiments, forexample, for use in an explicit negative limitation.

The term “contacting” refers to the act of touching, making contact, orof bringing to immediate or close proximity, including at the cellularor molecular level, for example, to bring about a chemical reaction or aphysical change, e.g., in a solution or in a reaction mixture.

An “effective amount” refers to an amount effective to bring about arecited effect, such as an amount necessary to form products in areaction mixture. Determination of a effective amount is typicallywithin the capacity of persons skilled in the art, especially in lightof the detailed disclosure provided herein. The term “effective amount”is intended to include an amount of a compound or reagent describedherein, or an amount of a combination of compounds or reagents describedherein, e.g., that is effective to form products in a reaction mixture.Thus, an “effective amount” generally means an amount that provides thedesired effect.

The term “alkyl” refers to a branched or unbranched hydrocarbon having,for example, from 1-20 carbon atoms, and often 1-12, 1-10, 1-8, 1-6, or1-4 carbon atoms. Examples include, but are not limited to, methyl,ethyl, 1-propyl, 2-propyl (iso-propyl), 1-butyl, 2-methyl-1-propyl(isobutyl), 2-butyl (sec-butyl), 2-methyl-2-propyl (t-butyl), 1-pentyl,2-pentyl, 3-pentyl, 2-methyl-2-butyl, 3-methyl-2-butyl,3-methyl-1-butyl, 2-methyl-1-butyl, 1-hexyl, 2-hexyl, 3-hexyl,2-methyl-2-pentyl, 3-methyl-2-pentyl, 4-methyl-2-pentyl,3-methyl-3-pentyl, 2-methyl-3-pentyl, 2,3-dimethyl-2-butyl,3,3-dimethyl-2-butyl, hexyl, octyl, decyl, dodecyl, and the like. Thealkyl can be unsubstituted or substituted, for example, with asubstituent described below. The alkyl can also be optionally partiallyor fully unsaturated. As such, the recitation of an alkyl group caninclude both alkenyl and alkynyl groups. The alkyl can be a monovalenthydrocarbon radical, as described and exemplified above, or it can be adivalent hydrocarbon radical (i.e., an alkylene).

The term “substituted” indicates that one or more hydrogen atoms on thegroup indicated in the expression using “substituted” or “optionallysubstituted” is replaced with a “substituent”. The number referred to by‘one or more’ can be apparent from the moiety on which the substituentsreside. For example, one or more can refer to, e.g., 1, 2, 3, 4, 5, or6; in some embodiments 1, 2, or 3; and in other embodiments 1 or 2, andif the substituent is an oxo group, two hydrogen atoms are replace bythe presence of the substituent. The substituent can be one of aselection of indicated groups, or it can be a suitable group recitedbelow or known to those of skill in the art, provided that thesubstituted atom's normal valency is not exceeded, and that thesubstitution results in a stable compound. Suitable substituent groupsinclude, e.g., alkyl, alkenyl, alkynyl, alkoxy, halo, haloalkyl,hydroxy, hydroxyalkyl, aryl, aroyl, (aryl)alkyl (e.g., benzyl orphenylethyl), heteroaryl, heterocycle, cycloalkyl, alkanoyl,alkoxycarbonyl, alkylcarbonyloxy, amino, alkylamino, dialkylamino,trifluoromethyl, trifluoromethoxy, trifluoromethylthio, difluoromethyl,acylamino, nitro, carboxy, carboxyalkyl, keto, thioxo, alkylthio,alkylsulfinyl, alkylsulfonyl, arylsulfinyl, arylsulfonyl,heteroarylsulfinyl, heteroarylsulfonyl, heterocyclesulfinyl,heterocyclesulfonyl, phosphate, sulfate, hydroxyl amine, hydroxyl(alkyl)amine, and cyano, as well as the moieties illustrated in theschemes and Figures of this disclosure, and combinations thereof.Additionally, suitable substituent groups can be, e.g., —X, —R, —O⁻,—OR, —SR, —S⁻, —NR₂, —NR₃, ═NR, —CX₃, —CN, —OCN, —SCN, —N═C═O, —NCS,—NO, —NO₂, ═N₂, —N₃, —NC(═O)R, —C(═O)R, —C(═O)NRR, —S(═O)₂O⁻, —S(═O)₂OH,—S(═O)₂R, —OS(═O)₂OR, —S(═O)₂NR, —S(═O)R, —OP(═O)(OR)₂, —P(═O)(OR)₂,—OP(═O)(OH)(OR), —P(═O)(OH)(OR), —P(═O)(O⁻)₂, —P(═O)(OH)₂, —C(═O)R,—C(═O)X, —C(S)R, —C(O)OR, —C(O)O⁻, —C(S)OR, —C(O)SR, —C(S)SR, —C(O)NRR,—C(S)NRR, or —C(NR)NRR, where each X is independently a halogen(“halo”): F, Cl, Br, or I; and each R is independently H, alkyl, aryl,(aryl)alkyl (e.g., benzyl), heteroaryl, (heteroaryl)alkyl, heterocycle,heterocycle(alkyl), or a protecting group. As would be readilyunderstood by one skilled in the art, when a substituent is keto (═O) orthioxo (═S), or the like, then two hydrogen atoms on the substitutedatom are replaced. In some embodiments, one or more of the substituentsabove can be excluded from the group of potential values forsubstituents on the substituted group. The various R groups in theschemes and figures of this disclosure can be one or more of thesubstituents recited above, thus the listing of certain variables forsuch R groups (including R¹, R², R³, etc.) are representative and notexhaustive, and can be supplemented with one or more of the substituentsabove.

The term “alkoxy” refers to the group alkyl-O—, where alkyl is asdefined herein. Examples of alkoxy groups include, but are not limitedto, methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, tert-butoxy,sec-butoxy, n-pentoxy, n-hexoxy, 1,2-dimethylbutoxy, and the like. Thealkoxy can be unsubstituted or substituted.

The term “acyloxy” refers to groups of the formula —O—C(═O)R, wherein Ris an alkyl group as previously defined. Examples of acyloxy groupsinclude acetoxy and propanoyloxy. The acyloxy can be unsubstituted orsubstituted. For example, the C1 (carbonyl) group of the acyloxy can besubstituted with an aryl group, such as phenyl, to provide anaryl-substituted acyloxy, such as a benzoyl group.

The term “alcohol” refers to an at least mono-hydroxy-substitutedalkane. A typical alcohol comprises a (C₁-C₁₂)alkyl moiety substitutedat a hydrogen atom with one or more hydroxyl group. Alcohols includemethanol, ethanol, n-propanol, i-propanol, n-butanol, butanol,s-butanol, t-butanol, n-pentanol, i-pentanol, hexanol, cyclohexanol,heptanol, octanol, nonanol, decanol, and the like. The carbon atom chainin alcohols can be straight, branched or cyclic. Alcohols can bemono-hydroxy, di-hydroxy, tri-hydroxy, and the like, as would be readilyrecognized by one of skill in the art.

A “monosaccharide” refers to any of the class of five-carbon orsix-carbon sugars. Examples of monosaccharides include six-carbonpolyols having the general chemical formula C₆H₁₂O₆. These compoundsinclude aldohexoses which have an aldehyde functional group at position1 or ketohexoses which have a ketone functional group at position 2.Example aldohexoses include allose, altrose, glucose, mannose, gulose,idose, galactose, and talose, in either D or L form.

Biorefining intermediates, such as reactants for an aldehyde couplingprocess, include 5-hydroxymethylfurfural (HMF) and relatedintermediates, such as furfural and other aldehyde (CHO)-containingorganic compounds that can be derived from (bio)renewable resources suchas cellulosic biomass.

Upgraded biofuel intermediates and liquid biofuels, such as products ofthe coupling reaction described herein, include compounds such as5,5′-di(hydroxymethyl)furoin (DHMF, C₁₂), the product of upgrading HMF(C₆); DF (the coupling product of furfural); the coupling product of HMFand furfural; the coupling products of HMF with furaldehydes such asthose of Formula X and other related furaldehydes; and furoins withdifferent numbers of carbons and substitution patterns, depending on thestarting material.

Products of the coupling reaction described herein, referred to as“coupling products” or “fuel intermediates” can be the furoin productsresulting from the direct condensation (coupling) of two furaldehydes.The coupling can be made between the two same furaldehydes(homo-coupling) or two different furaldehydes (cross-coupling). Thetotal number of carbons in the coupling products is the sum of the twofuraldehydes employed, for example, homocoupling of the C₆ HMF forms C₁₂5,5′-di(hydroxymethyl)furoin (DHMF).

The term “furaldehydes” refers to biomass-derived furan aldehydesincluding, but not limited to, furfural (C₅), 5-methylfurfural (C₆),5-hydroxymethylfurfural (HMF, C₆), and other aldehyde (CHO)-containingfurans that can be derived from (bio)renewable resources such ascellulosic biomass. Furaldehydes and furaldehyde derivatives includecompounds of Formula X:

wherein each R is independently, for example, hydrogen, halo, hydroxy,nitro, amino, alkylamino, dialkylamino, (C₁-C₁₂)alkyl,hydroxy-(C₁-C₁₂)alkyl, acyl-(C₁-C₁₂)alkyl,(C₁-C₁₂)alkylcarbonyl-(C₁-C₁₂)alkyl, and carboxy-(C₁-C₁₂)alkyl, such as5-hydroxymethylfurfural and furfural and substituted compounds thereof.

“Oxygenated diesel fuels” include polyols derived from hydrogenation ofthe coupling products. Examples include DHMF ethers derived fromacid-catalyzed etherification of DHMF with ethanol and other alcohols,including mono-, di- and tri-ethers of DHMF and mixtures thereof; DHMFesters from esterification of DHMF with alkanoic acids or alkanoicanhydrides such as propionic anhydride, including mono-, di-, andtri-esters of DHMF and mixtures thereof.

A “high-quality hydrocarbon fuel” refers to a mixture of alkanes(linear, branched or cyclic) that can be used as a fuel source.Preferably, the alkanes are liquid and include about 10 to about 22carbon atoms. The fuel can be derived from hydrodeoxygenation of thecoupling products described herein. Preferably, the alkane mixture has anarrow alkane distribution and linear structure, and contains negligibleor a minimum amount of oxygenated species. Narrow alkane distributioncompounds can be prepared having precisely 8, 9, 10, 11, 12, 13, 14, 15,16, 17, 18, 19, 20, 21, or 22 carbons, or ranges in between any two ofthe forgoing integers (e.g., 8-12, 10-16, 8-14, 12-20, 10-18, 16-22,etc.), especially 2-3 carbon ranges such as 10-12, 11-13, 12-14, 13-15,14-16, and the like. In some embodiments, the fuel is absent ofdetectable amounts of sulfur.

An “ionic liquid” refers to a salt in the liquid state at ambienttemperatures (for example, at least a liquid between 5° C. and 30° C.,typically a liquid over a range of more than 100° C.), wherein the saltis composed of ions and/or short-lived ion pairs. Typically, an ionicliquid (IL) has a melting point below about 100° C. (212° F.). Usefulcations of an ionic liquid that are useful in this invention are furtherdescribed below. Useful anions for ionic liquids include acetate,halides including fluoride, chloride, bromide, and iodide, chlorate,nitrate, triflate, tosylate, tetrachloaluminate, tetrafluoroborate,hexafluorophosphate, anions such as [⁻OH], [⁻NTf₂], [⁻N(CN)₂], [CH₃SO₃⁻], [HCO₂ ⁻], [—OC(═O)C(OH)Me], [HSO₄ ⁻], [HCO₃ ⁻], and the like.

A “noble metal” refers to a metal that is resistant to corrosion andoxidation in moist air, including copper, ruthenium, rhodium, palladium,silver, osmium, iridium, platinum, and gold. Noble metals can be used toaid reduction reactions, for example, in combination with an acid and ahydrogen gas atmosphere, and optionally with added heat.

Methods of the Invention

Biomass resources such as cellulose and glucose can be converted intoHMF and other bio-refining intermediates by a variety of knowntechniques. See for example, the techniques described in Example 1below, and U.S. Pat. No. 7,572,925 (Dumasic et al.). Bio-refiningintermediates can be upgraded into biofuels and related intermediates bythe organocatalytic methods described herein. One such method of theinvention can be carried out by self-condensation (coupling) of HMFand/or other aldehyde-containing bio-refining intermediates, as well ascross-condensation (coupling) of two or more different intermediates, inthe presence of a catalytic amount of a suitable and effective catalyst,at ambient temperature up to about 160° C., often at 60-80° C.Self-condensation of HMF cleanly provides 5,5′-di(hydroxymethyl)furoin(DHMF) in high yield. This product and others can be further efficientlyconverted into hydrocarbon fuels.

A variety of catalysts can be used to facilitate the coupling reactionsas follows.

(a) Catalytic ionic liquids containing the acetate anion, such as1-alkyl(R)-3-methyl(M)imidazolium(IM) acetate salts, [RMIM]OAc, whichcan self-release N-heterocyclic carbene (NHC) catalysts under theupgrading reaction conditions. A large number of different cations maybe used. Typical nitrogen- or sulfur-based cations are acceptable, suchas: 1-alkyl-3-methylimidazolium, 1-alkyl-3-alkylpyridinium (where thealkyl groups need not be the same), trialkylsulfonium, alkyl oraryl-substituted thiazolium salts, 1-alkyl-1-methylpyrrolidinium,1,2-dialkylpyrazolium, dialkylmorpholinium, guanidinium, and2-alkyl-isoquinolinium.

(b) Discrete NHCs such as1,3,4-triphenyl-4,5-dihydro-1H-1,2,4-triazol-5-ylidene (TPT),1,3-di-mesityl-butyl-imidazolin-2-ylidene (IMes),1,3-dialkylimidazolin-2-ylidene, and other related NHC and carbenespecies. Other discrete NHCs derived from salts of dialkyl or diarylimidazolium, aryl substituted triazolium, and alkyl or aryl substitutedthiazolium, can also be used for the coupling reaction.

(c) 1-Alkyl(R)-3-methyl(M)imidazolium(IM) chloride salts, [RMIM]Cl, inthe presence of an organic or inorganic base such as DBU(1,8-diazabicyclo[5.4.0] undec-7-ene) or an alkali metal alkoxide suchas KOtBu, which can deprotonate C2-H protons under the reactionconditions to generate the carbene catalyst in situ. Other suitablebases include alkali metal hydrides such as NaH or KH, or an alkalimetal hexamethyldisilazane such as potassium hexamethyldisilazane(KHMDS).

Conversion of the condensation (coupling) products into liquid jet fuel,various different grades of biofuels, polyols, or oxygenated dieselfuels, can be carried out by chemical transformations such ashydrogenation, dehydration, etherification, esterification, and variouscombinations thereof. Examples of these transformations include: (a)hydrogenation of DHMF into DHM-THF-EG; (b) etherification of DHMF intoethers of DHMF including, for example, mono-, di- and tri-ethers ofDHMF; and (c) esterification of DHMF to esters of DHMF including, forexample, mono-, di-, and tri-esters of DHMF. Common hydrogenationcatalysts such as Pd/C can be employed for hydrogenation, and commonacids, including solid acids, can be used for etherification. In oneembodiment, the condensation (coupling) product DHMF can be convertedinto premium alkane fuels by hydrodeoxygenation in the presence of abifunctional metal-acid catalyst. Bifunctional catalysts are those withboth metal and acid sites (e.g., noble metal on acidic support).Specific examples of bifunctional catalysts include Pt/CsH₂PW₁₂O₄₀, andPt/C with TaOPO₄.

Accordingly, in one embodiment, the invention provides a compound ofFormula I:

wherein each R¹ is independently H, OH, halo, nitro, amine, alkylamino,dialkylamino, alkoxy, or acyloxy; and R² is OH, halo, nitro, amine,alkylamino, dialkylamino, alkoxy, or acyloxy; provided that at least oneR¹ is not H. In another embodiment, the 3- or 4-position of a furan ringof Formula (I) can be substituted as described for Formula (X). Thecompound can be a mono-, di-, or tri-ether, or a mono-, di-, ortri-ester. Thus, compounds of Formula (I) can be, for example, compoundsof Formula (IA), (IB), or (IC):

wherein each R is independently aryl or (C₁-C₁₂)alkyl, where the alkylcan be straight, branched, or cyclic, and the alkyl and/or aryl can beoptionally substituted as described above for the definition ofsubstituted, or an R¹ as defined for Formula (I). Specific examples ofcompounds of Formulas (I), (IA), and (IB) include:

In another embodiment, the invention provides compounds of Formula II:

wherein R¹ is H, OH, halo, amine, alkylamino, dialkylamino, alkoxy, oracyloxy; and R² is H, OH, halo, amine, alkylamino, dialkylamino, alkoxy,or acyloxy. In some embodiments, at least one R¹ is not H. In variousembodiments, at least one R² is not H. In certain embodiments, at leastone R² is not OH.

Compounds of Formula (II) can be, for example, compounds of Formulas(IIA), (IIB), or (IIC):

wherein each R is independently H, alkyl, or acyl, or R¹ as defined forFormula (II) above. Thus, the compound can be a mono-, di-, tri-, ortetra-ether (e.g., Formula IIA), or a mono- or di-ether (e.g., FormulaIIB or IIC). The compounds can also be mono-, di-, tri-, or tetra-esters(e.g., Formula IIA), or mono- or di-esters (e.g., Formula IIB or IIC).Specific examples of Formulas (II), (IIA), (IIB), or (IIC) include:

As to any of the formula and structures above, any available hydroxygroup, R, R¹, or R² can be, or can be converted to, an ether or an estermoiety. Accordingly, a variety of monoethers, diethers, triethers,tetraethers, monoesters, diesters, triesters, and tetraesters can beprovided. Additionally, compounds that include both ether and estermoieties can be prepared, by controlling the order and stoichiometry ofreaction conditions, as can be determined by one of skill in the art.

Under oxidative work-up conditions, for example, with air-oxidation,added oxidants, or the like, compounds of Formula (III) and (IV) canalso be prepared:

wherein each R¹ is independently H, OH, halo, nitro, amine, alkylamino,dialkylamino, alkoxy, or acyloxy. In some embodiments, at least one R¹is not H, and/or at least one R¹ is not OH. In various embodiments, the3- or 4-position of a furan ring of Formula (I) can be substituted asdescribed for Formula (X).

By carrying out a selective hydrogenation reaction on Formula (I) or(II), for example, with additional heat or under longer reaction timesfor the preparation of Formula (II), a compound of Formula (IV) can beprepared, where one R² is at least initially OH:

wherein each R¹ is independently H, OH, halo, nitro, amine, alkylamino,dialkylamino, alkoxy, or acyloxy; and each R² is independently OH, halo,nitro, amine, alkylamino, dialkylamino, alkoxy, or acyloxy. In someembodiments, at least one R¹ is not H, and/or at least one R¹ is not OH.In another embodiment, the 3- or 4-position of a furan ring of Formula(I) can be substituted as described for Formula (X).

Compounds and formulas above that include a hydroxymethyl group at afuran or tetrahydrofuran 5- or 5′-position can be modified to oxidizethe hydroxymethyl group to a carbonyl moiety, substituted by a hydroxyl,alkoxy, or amino group using known oxidative transformations. As wouldbe recognized by one of skill in the art, amino groups can be optionallyprotected, for example, with a nitrogen protecting group such asacetate, benzyl, benzyloxy, and the like.

The invention further provides a composition comprising one or morecompounds or compounds of a formula described above, in combination withone or more (C₈-C₂₂)alkanes, or (C₁₀-C₂₂)alkanes.

The invention also provides an organocatalytic method to couple a firstfuraldehyde compound, such as a compound of Formula (X), and a secondfuraldehyde compound, such as a second compound of Formula (X). Thecompounds can be the same or different. The method can includecontacting a first furaldehyde compound and a second furaldehydecompound in the presence of an ionic liquid under conditions where theionic liquid forms an N-heterocyclic carbene (NHC), or by contacting thefuraldehydes in the presence of a discrete NHC, to provide a coupledproduct, such as a compound that includes a (C₁₀-C₁₂)furoin moiety. Insome embodiments, the product will include a substituent at a furan5-position, such as hydroxymethyl. In other embodiments, the product caninclude substituents at both the 5-position and the 5′-positions of thecoupled furan products. The furans can be substituted on the furan ringat the 3, 4, 3′, or 4′ positions. The hydroxy group of a hydroxymethylgroup at the 5-position and/or the 5′-position can further be modified,as described herein, such as by oxidation, conjugation, or reduction.

In another embodiment, the invention provides an organocatalytic methodto homocouple 5-hydroxymethylfurfural (HMF) comprising contacting HMFand an ionic liquid under conditions wherein the ionic liquid forms anN-heterocyclic carbene (NHC), or by contacting HMF and a discrete NHC,to provide 5,5′-di(hydroxymethyl)furoin (DHMF).

The ionic liquid cation can be a 1-alkyl-3-methylimidazolium,1-alkyl-3-alkylpyridinium, trialkylsulfonium, alkyl-substitutedthiazolium, aryl-substituted thiazolium, 1-alkyl-1-methylpyrrolidinium,1,2-dialkylpyrazolium, dialkylmorpholinium, guanidinium, or2-alkyl-isoquinolinium. For ionic liquid cations, each alkyl can beindependently (C₁-C₁₂)alkyl, for example, methyl, ethyl, propyl, orbutyl. Aryl can be as defined for aryl above, for example, phenyl.Anions of the ionic liquid can be acetate, halide, or an anion asdescribed above in the definition of ionic liquids. Any suitable andeffective combination of cation and anion that facilitates the umpolungcoupling of furaldehydes can be employed.

In one embodiment, the ionic liquid can be a1-alkyl-3-methyl-imidazolium halide salt in the presence of an organicor inorganic base, wherein the base is capable of deprotonating a C2-Hproton of the ionic liquid under the reaction conditions to generate acarbene catalyst in situ. For example, the ionic liquid can be a1-alkyl-3-methyl-imidazolium acetate salt. In certain specificembodiments, the ionic liquid is [EMIM]OAc, or [EMIM]Cl in the presenceof a base. The base can be, for example, DBU, an alkali metal alkoxide,an alkali metal hydride, or an alkali metal hexamethyldisilazane.Specific examples include NaOMe, KOMe, NaOtBu, KOtBu, LiH, NaH, KH,NaHMDS, or KHMDS.

A variety of different discrete NHCs can be employed in the methodsdescribed herein. Examples of such discrete NHCs include salts ofdialkyl or diaryl imidazolium, aryl substituted triazolium, and alkyl oraryl substituted thiazolium. In one embodiment, the discrete NHC is1,3,4-triphenyl-4,5-dihydro-1H-1,2,4-triazol-5-ylidene (TPT). In anotherembodiment, the discrete NHC is1,3-di-mesityl-butyl-imidazolin-2-ylidene (IMes). In another embodiment,the discrete NHC is a 1,3-dialkylimidazolin-2-ylidene.

After the coupling product has formed, the product can be furthermodified by hydrogenation, hydrogenolysis, hydrodeoxygenation,etherification, esterification, or combinations thereof. The productscan be used as liquid fuels.

For example, the invention provides for hydrogenating DHMF to provide aliquid comprising 1,2-di(5-hydromethyltetrahydrofuran-2-yl)ethyleneglycol. The product can be conjugated to provide mono-, di-, ortri-ethers, mono-, di-, or tri-esters, or combinations of such moietieson the product of the reaction.

An organic solvent can be used in the coupling reaction. However, theionic liquid can also act as a solvent for the reaction system. Thus,the method can be carried out under otherwise solvent-free conditions,or in the absence of an organic solvent.

The invention further provides a method to prepare a (C₈-C₂₂)alkane, ora (C₁₀-C₂₂)alkane, comprising contacting a compound of Formula I:

wherein each R¹ and R² is as defined for Formula (I) above; or

contacting a compound of Formula II

wherein R¹ and R² can be as described above for Formula (II); with abifunctional catalyst systems that comprises a noble metal, such aspalladium or platinum metal, and an acidic moiety under reactionconditions comprising heat and H₂ pressure in water; thereby reducingthe compound of Formula (I) or (II) to provide one or more(C₈-C₂₂)alkanes or one or more (C₁₀-C₂₂)alkanes. The acidic moiety canbe, for example, a liquid or solid acid. In some embodiments, at leastone R¹ of Formula (I) or Formula (II) is not H. In some embodiments, theproduct is exclusively a hydrocarbon.

The method above can also be used to prepare compounds of Formula (IV),where the carbonyl of the intermediate is selectively reduced over thearomatic furan rings. Thus, in some embodiments, the product can includeno more than 1, 2, 3, 4, 5, 6, 7, or 8 oxygen atoms per productmolecule, depending on the reaction conditions employed and the desiredproducts of the reaction.

In one specific embodiment, the compound of Formula (I) is5,5′-di(hydroxymethyl)furoin (DHMF). In some embodiments, thebifunctional catalyst system is an acidic aqueous solution of aninorganic acid and a noble metal. The noble metal can provide supportfor the acid, or the noble metal can be adsorbed onto carbon black(e.g., metal/C). In some embodiments, the bifunctional catalyst systemis an acidic solution of aqueous H₃PO₄ and Pd/C; a heteropoly acid ofthe formula CsH₂PW₁₂O₄₀ supported Pt; or an acidic solid catalyst of theformula TaOPO₄ in combination with Pt/C.

In one specific embodiment, the compound of Formula (I) is5,5′-di(hydroxymethyl)furoin (DHMF), the bifunctional catalyst system isan acidic solid catalyst of the formula TaOPO₄ in combination with Pt/C,wherein (C₁₀-C₂₂)alkanes are produced with at least 90% selectivity.

Suitable temperatures for use with the bifunctional catalyst include atleast about 150° C., at least about 175° C., at least about 200° C., atleast about 250° C., or at least about 275° C. For example, suitabletemperature ranges include about 150° C. to about 350° C., about 200° C.to about 325° C., about 250° C. to about 325° C., or about 300° C. Lowertemperatures typically merely require longer reaction times. Thereaction with the bifunctional catalyst can be carried out under anysuitable and effective pressure of hydrogen gas, such as at least about1.5 MPa, as at least about 1.7 MPa, as at least about 2 MPa, as at leastabout 2.5 MPa, or at about 3 MPa. Greater pressures of hydrogen gas canbe employed to further shorten reaction time. Lesser pressures ofhydrogen gas can be employed but typically require longer reactiontimes.

General Synthetic Methods

The invention provides methods of making the compounds and compositionsof the invention. The compounds and compositions can be prepared by anyof the applicable techniques described herein, optionally in combinationwith standard techniques of organic synthesis. Many techniques such asetherification and esterification are well known in the art. However,many of these techniques are elaborated in Compendium of OrganicSynthetic Methods (John Wiley & Sons, New York), Vol. 1, Ian T. Harrisonand Shuyen Harrison, 1971; Vol. 2, Ian T. Harrison and Shuyen Harrison,1974; Vol. 3, Louis S. Hegedus and Leroy Wade, 1977; Vol. 4, Leroy G.Wade, Jr., 1980; Vol. 5, Leroy G. Wade, Jr., 1984; and Vol. 6; as wellas standard organic reference texts such as March's Advanced OrganicChemistry: Reactions, Mechanisms, and Structure, 5^(th) Ed., by M. B.Smith and J. March (John Wiley & Sons, New York, 2001); ComprehensiveOrganic Synthesis. Selectivity, Strategy & Efficiency in Modern OrganicChemistry. In 9 Volumes, Barry M. Trost, Editor-in-Chief (PergamonPress, New York, 1993 printing); Advanced Organic Chemistry, Part B:Reactions and Synthesis, Second Edition, Cary and Sundberg (1983);Protecting Groups in Organic Synthesis, Second Edition, Greene, T. W.,and Wutz, P. G. M., John Wiley & Sons, New York; and ComprehensiveOrganic Transformations, Larock, R. C., Second Edition, John Wiley &Sons, New York (1999).

A number of exemplary methods for preparation of compounds andcompositions of the invention are provided below. These methods areintended to illustrate the nature of such preparations are not intendedto limit the scope of applicable methods.

Generally, the reaction conditions such as temperature, reaction time,solvents, work-up procedures, and the like, will be those common in theart for the particular reaction to be performed. The cited referencematerial, together with material cited therein, contains detaileddescriptions of such conditions. Typically the temperatures will be−100° C. to 400° C., as necessary for the reaction of interest, solventsif required will be aprotic or protic depending on the conditionsrequired, and reaction times can be about 1 minute to about 10 days.Work-up typically consists of quenching any unreacted reagents followedby partition between a water/organic layer system (extraction) andseparation of the layer containing the product of interest.

Oxidation and reduction reactions are typically carried out attemperatures near room temperature (about 23° C.), although for metalhydride reductions frequently the temperature is reduced to 0° C. to−100° C. Heating can also be used when appropriate to facilitatecompletion of the reaction or to increase conversion of substrates.Solvents are typically aprotic for reductions and may be either proticor aprotic for oxidations. Reaction times are adjusted to achievedesired conversions.

The formulas and compounds described herein can be modified usingprotecting groups. Suitable amino and carboxy protecting groups areknown to those skilled in the art (see for example, T. W. Greene,Protecting Groups In Organic Synthesis; Wiley: New York, Third Edition,1999, and references cited therein; Philip J. Kocienski; ProtectingGroups (Georg Thieme Verlag Stuttgart, New York, 1994); and referencescited therein).

Ionic liquids and their reactions are further described in the referenceliterature. These known techniques and conditions can be used to carryout and modify reactions and compounds described herein. Usefulinformation has been described by, for example, Wasserscheid and Keim,Angew. Chem Int Ed. 2000, 39, 3772; Welton, Chem. Rev. 1999, 99, 2071,Ionic Liquids in Synthesis, Wasserscheid and Welton, Eds., Wiley-VCH(2002); and Molten Salt Chemistry, Mamantov and Marassi, Eds., NATO ASISeries C, Mathematical and Physical Sciences Vol. 202, D. ReidelPublishing Co. (1986); and references cited therein.

The following Examples are intended to illustrate the above inventionand should not be construed as to narrow its scope. One skilled in theart will readily recognize that the Examples suggest many other ways inwhich the invention could be practiced. It should be understood thatnumerous variations and modifications may be made while remaining withinthe scope of the invention.

EXAMPLES

Materials, Reagents, and Methods

Syntheses and manipulations of air- and moisture-sensitive materialswere carried out in flamed Schlenk-type glassware on a dual-manifoldSchlenk line, on a high-vacuum line, or in an inert gas (Ar orN₂)-filled glovebox. HPLC-grade organic solvents were first spargedextensively with nitrogen during filling 20 L solvent reservoirs andthen dried by passage through activated alumina (for Et₂O, THF, andCH₂C₁₂) followed by passage through Q-5 supported copper catalyst (fortoluene and hexanes) stainless steel columns. HPLC-grade DMF wasdegassed and dried over CaH₂ overnight, followed by vacuum distillation(CaH₂ was removed before distillation). DMSO-d₆ was first degassed anddried over CaH₂, followed by vacuum distillation. NMR-scale reactionswere conducted in Teflon-valve-sealed J. Young-type NMR tubes withhexamethylbenzene as the internal standard. NMR spectra were recorded ona Varian Inova 300 (FT 300 MHz, ¹H; 75 MHz, ¹³C) or a Varian Inova 400MHz spectrometer. Chemical shifts for ¹H and ¹³C spectra were referencedto internal NMR solvent residual resonances and are reported as partsper million relative to SiMe₄.

High-resolution mass spectrometry (HRMS) data were collected on anAgilent 6220 Accurate time-of-flight LC/MS spectrometer. Elementalanalyses were carried out by Robertson Microlit Laboratories, Madison,N.J.

The water-soluble products were analyzed by Agilent 1260 Infinity HPLCsystem equipped with either an Agilent Eclipse Plus C18 Column (100×4.6mm; 80/20 water/methanol, 0.6 ml/min, 30° C.) with a UV detector (284nm) for 5-hydroxymethylfurfural (HMF) and 5,5′-di(hydroxymethyl)furoin(DHMF) detection and quantification, or a Biorad Aminex HPX-87H Column(300×7.8 mm; water, 0.6 ml/min, 45° C.) with an Agilent 1260 InfinityELSD detector (65° C., 3.5 bar, gain 6) for glucose and other sugarsdetection.

Hydrogenation and HDO reactions were carried out in a Parr 4842 pressurereactor (Parr Instrument Co.). The organic products extracted bydichloromethane (DCM) were analyzed either by an Agilent 6890N GC-FIDsystem with a Durabond DB-5 ms column (30 m, 0.25 mm I.D., 0.25 μm film)or by an Agilent 6890 GC-MS system equipped with a Phenomenex ZebronZB-5 ms column (30 m, 0.25 mm I.D., 0.25 μm film). Heating values weremeasured by a Petrolab C2000 calorimeter. Any DHMF remained in the waterphase after HDO was analyzed with an Agilent Eclipse Plus C18 Column(100×4.6 mm; 80/20 water/methanol, 0.6 mL/min, 30° C.) and a UV detector(284 nm).

D-Glucose (Granular powder, Fisher Chemical), CrCl₂ (Alfa Aesar), HMF(Acros Organics), hexamethylbenzene (Alfa Aesar), 1,8-diazabicyclo[5.4.0] undec-7-ene (DBU, Acros Organics), acetic acid (MallinckrodtChemicals, ACS grade), silver acetate (Strem Chemical) were used asreceived. N-Heterocyclic carbenes (NHCs),1,3-bis(2,4,6-trimethyl-phenyl)imidazol-2-ylidene (IMes) and1,3-di-tert-butylimidazol-2-ylidene (I^(t)Bu), were purchased from StremChemical Co. Literature procedures were used to prepare1,3,4-triphenyl-4,5-dihydro-1H-1,2,4-triazol-5-ylidene (TPT) (Enders etal., Angew. Chem., Int. Ed. Engl. 1995, 34, 1021; Enders et al.,Synthesis 2003, 1292-1295), while 1-ethyl-2,3-dimethylimidazoliumacetate ([EDMIM]OAc) (Brandt et al., Green Chem. 2010, 12, 672-679) wasprepared using an anion exchange route (vide infra).1-Ethyl-3-methylimidazolium acetate ([EMIM]OAc, Aldrich) and1-ethyl-2,3-dimethylimidazolium chloride ([EDMIM]Cl, Aldrich) were driedunder vacuum at 100° C. for 24 hours. 1-Ethyl-3-methylimidazoliumchloride ([EMIM]Cl, Fluka) was dried under vacuum at 100° C. for 24hours, followed by repeated recrystallization from CH₂Cl₂ and hexanes atroom temperature. The purified ionic liquids were stored in anargon-filled glovebox.

Additionally, furfural (Alfa Aesar), 5-methylfurfural (MF, Alfa Aesar),5-hydroxymethylfurfural (HMF, Acros Organics), H₃PO₄ (85 wt % aqueoussolution, Sigma Aldrich), Ta₂O₅ (Alfa Aesar), Cs₂CO₃ (Alfa Aesar),H₃PW₁₂O₄₀.xH₂O (Alfa Aesar), PtCl₄ (Acros Organics), Pd/C and Pt/C (5 wt%, Alfa Aesar), and 1,3-bis(2,4,6-trimethylphenyl)-1,3-dihydro-2H-imidazol-2-ylidene (IMes) (SigmaAldrich) were purchased and used as received. TaOPO₄ andCs_(x)H_(3-x)PW₁₂O₄₀ (x=1 and 2.5) were prepared according to literatureprocedures (Huang et al., RSC Advances, 2012, 2, 11211; Tian et al.,Chem. Eng. Technol. 2011, 34, 482). The supported 4 wt %Pt/Cs_(x)H_(3-x)PW₁₂O₄₀ catalyst was prepared by incipient wetnessimpregnation, which was dried in an oven at 120° C. overnight andreduced under flowing H₂ (100 mL/min) at 250° C. for 3 hours before use.

Example 1. Conversion of Biorefining Intermediates to Value-AddedChemicals

The acetate-based room-temperature (RT) IL, [EMIM]OAc, has beenidentified as a better solvent than chloride-based ILs for biomasssolution processing (i.e., dissolution, fractionation, andre-precipitation), due to its lower melting point, viscosity andcorrosive character as well as higher loading and non-toxicity. However,for biomass conversion into sugars and HMF, the chloride-based ILs suchas [RMIM]Cl (R=Et, ^(n)Bu) are preferred solvents, and we have found[EMIM]OAc is completely ineffective for the glucose (orcellulose)-to-HMF conversion (Liu and Chen, Appl. Catal. A: Gen. 2012,435/436, 78). A recent report disclosed that [EMIM]OAc rapidly degradesHMF (>99% degradation at 100° C. after 8 h), but the degradationmechanism was not proposed and the degradation product was notidentified (Stahlberg et al., Green Chem. 2010, 12, 321).

We found that [EMIM]OAc also rapidly degrades glucose (70% degradationat 100° C. after 1 hour), as described below. We therefore hypothesizedthat the observed rapid HMF degradation in [EMIM]OAc may be rendered byN-heterocyclic carbene (NHC) catalysis, because it is known that a smallconcentration of carbene exists in this IL with the basic acetate anion,as demonstrated experimentally by its carbene-type reaction withelemental sulfur or selenium and as catalyst for benzoin condensation ofbenzaldehyde. While addressing the mechanism of HMF degradation in[EMIM]OAc, we discovered that this “harmful” degradation process can beutilized for highly efficient upgrading of HMF into a high-valuebiorefinery product, 5,5′-di(hydroxymethyl)furoin (DHMF)—a kerosene/jetfuel intermediate, through NHC-catalyzed self-condensation enabled bythis organocatalytic IL. Subsequent use of a discrete NHC (1-5 mol %),the Enders triazolylidene carbene TPT(1,3,4-triphenyl-4,5-dihydro-1H-1,2,4-triazol-5-ylidene) (Enders et al.,Synthesis 2003, 1292-1295), leads to rapid (1 h), highly selective andhigh-yield synthesis of DHMF from HMF. The in situ generated NHC bytreating the chloride-based IL [EMIM]Cl with an organic base alsorapidly upgrades HMF into DHMF in high yield (96%).

HPLC monitoring of the HMF degradation in [EMIM]OAc (1:1 molar ratio) ina shaker revealed rapid degradation of HMF even at temperatures farbelow 120° C., a typical temperature employed for biomass conversion.For example, 70% and 94% of HMF has been degraded after 1 h at 50° C.and 80° C., respectively. The degradation kinetics at 80° C. wasexamined with NMR by performing the degradation in DMSO-d₆ in a J.Young-type NMR tube with a 1/1 HMF/[EMIM]OAc molar ratio and usinghexamethylbenzene as the internal standard. A first-order kinetic plotof the initial degradation process (2-15 minutes) yielded a rateconstant of k=0.085 min⁻¹ at 80° C., corresponding to a degradationhalf-life of 8.2 minutes at this temperature.

Parallel scale-up runs clearly showed formation of a new compound as thepredominant product (by HPLC, FIG. 1), with a yield of 72% at HMFconversion of 86% at 80° C. Subsequent separation and purificationafforded the pure compound (FIG. 1) in 50% isolated yield. This compoundis stable in water and air, as it was isolated from the aqueous mediumand no decomposition or oxidation was observed after exposing the solidsample to air for a week. NMR and MS data, detailed below, clearlyindicate it is a C₁₂ furoin, DHMF, the molecular structure of which hasbeen confirmed by X-ray diffraction analysis (FIG. 2).

Structural data clearly show a C═O double bond for C(6) with a bondlength of 1.224(7)Å and a CH—OH single bond for C(7) with a bond lengthof 1.420(10)Å, the latter of which is identical to the terminal CH₂—OHbond distance [e.g., C(12)-O(6)H=1.420(6)Å]. This assignment is furtherconfirmed by the sum of the angles around C(6) (carbonyl) and C(7)(hydroxyl) carbons of 360.1° and 332.3°, for sp²-hybridizedtrigonal-planar and sp³-hybridized tetrahedral carbon centers,respectively. CCDC-887451 contains the supplementary crystallographicdata for DHMF. These data can be obtained free of charge from TheCambridge Crystallographic Data Centre viawww.ccdc.cam.ac.uk/data_request/cif.

The identification and characterization of the structure of the mainproduct formed from the HMF degradation in [EMIM]OAc prompted us torealize that DHMF is the umpolung condensation product of HMF catalyzedby [EMIM]OAc. The catalytic cycle for this unique process enabled by theorganocatalytic [EMIM]OAc is proposed in FIG. 3 and the general reactionis shown below in Scheme 1.

The catalyst in this carbene catalysis is1-ethyl-3-methylimidazolin-2-ylidene carbene I (FIG. 3), present in the[EMIM]OAc equilibrium that favors the ion pair form. The early steps ofthe proposed elementary reactions involved in the catalysis deviatesomewhat from those put forth for the NHC-catalyzed umpolung ofaldehydes and α,β-unsaturated esters, due to the important role of HOAc,which co-exists with carbene I in the [EMIM]OAc equilibrium.Specifically, nucleophilic addition of the carbene I to the carbonylgroup of HMF generates a zwitterionic tetrahedral intermediate, which isprotonated by HOAc to afford a 2-(5-hydroxymethyl-2-α-hydroxyfuranyl)imidazolium acetate salt, the resting intermediate II.

Under elevated temperature, intermediate II is deprotonated by theacetate anion to form a nucleophilic enaminol (III′). Like the Breslowintermediate involved in the benzoin reaction (Breslow, J. Am. Chem.Soc. 1958, 80, 3719), this enaminol is the acyl anion equivalent (III),thus attacking the carbonyl group of a second HMF molecule to formanother tetrahedral intermediate (IV). Collapse of this tetrahedralintermediate, via proton transfer and elimination of I, produces DHMFand regenerates the NHC catalyst, thus closing the catalytic cycle (FIG.3). This proposed overall mechanism explains well the observed catalysisfor upgrading of HMF into DHMF by [EMIM]OAc and is consistent with thefour lines of evidence presented as follows.

First, previous studies have shown that a small concentration of carbeneexists in [EMIM]OAc, which is capable of executing carbene catalysis. Tofurther confirm this point, we replaced [EMIM]OAc with1-ethyl-2,3-dimethylimidazolium acetate, ([EDMIM]OAc, in which theacidic proton at C(2) of the imidazolium ring is substituted with themethyl group. As predicted, the carbene catalysis is completely shutdown and there is no conversion of HMF into DHMF, thereby supporting theproposed catalyst being the NHC released from [EMIM]OAc.

Second, on the basis of the proposed mechanism, ILs paired withnon-basic anions, which are incapable of self-releasing NHCs like[EMIM]OAc, should be ineffective for this carbene catalysis but could beactivated, with a strong organic base, to deliver the NHC catalyst andthus effect the same type of carbene catalysis. Indeed, [EMIM]Cl, whileitself is ineffective for this catalysis, becomes a highly effective HMFupgrading catalyst system, when treated with DBU(1,8-diazabicyclo[5.4.0] undec-7-ene) which generates the NHC catalystin situ. Thus, with a 5 mol % catalyst loading, which was controlled bythe amount of DBU added, DHMF was obtained in 96% yield (by HPLC) at 80°for 1 hour. Potential co-solvent effects were also examined, showing aminimal effect on DHMF yield.

Third, we obtained direct evidence for the formation of the restingintermediate II through NMR monitoring of the HMF reaction with[EMIM]OAc (1:1 molar ratio) in DMSO-d₆ at RT (˜22° C.) and 80° C. withhexamethylbenzene as the internal standard. At RT, 17% HMF was consumedimmediately upon mixing HMF with [EMIM]OAc, which approximatelycorresponds to the amount of the NHC catalyst accessible in [EMIM]OAc atthis temperature for its reaction with HMF to form intermediate II. Thisintermediate is not converted into DHMF at RT, even after 24 h. Withthis valuable information, next we carried out the same reaction at RTbut with a 1:5 molar ratio of HMF:[EMIM]OAc to form the intermediateexclusively (i.e., devoid of HMF and DHMF), plus excess [EMIM]OAc; thereaction in this ratio at RT enabled conclusive spectroscopiccharacterization of intermediate II (FIGS. 4 and 5).

At 80° C., on the other hand, FIG. 6 shows that intermediate II isformed instantaneously upon mixing HMF with [EMIM]OAc (1:1 ratio) and,as the reaction proceeds from 2 minutes to 25 minutes, a gradualconsumption of this intermediate and HMF, accompanied by concurrentformation of DHMF. Another experiment where heating the intermediate inthe absence of HMF led to formation of DHMF indicates that the reactionof NHC I with HMF to form intermediate II is reversible (i.e., releaseof HMF is needed to further convert II to DHMF at elevated temperature).Overall, these results demonstrate the formation of intermediate II isfast (and reversible), while the II-to-III step is rate-limiting andsubsequent steps in the catalytic cycle are also relative fast, asintermediates III and IV were not detectable en route to rapid formationof DHMF.

Fourth, if the small concentration of NHC I present in [EMIM]OAc is thecatalyst for self-condensation of HMF to DHMF, then the use of thepreformed, discrete NHCs should lead to even more rapid and efficientupgrading of HMF to DHMF. Indeed, with the Enders TPT being the catalyst(5 mol %), near quantitative (98% by NMR) conversion of HMF to DHMF wasobserved in THF at RT after 24 hours, resulting in a high isolated yield(86%; unoptimized) of DHMF. The rate of the TPT (5 mol %)-catalyzedcondensation of HMF can be greatly enhanced at elevated temperature. At60° C. for 1 hour, 94% DHMF (NMR yield) was achieved within 1 hour,accomplishing a 87% isolated (unoptimized) yield.

The performance of the two Arduengo carbenes,1,3-di-tert-butylimidazolin-2-ylidene (I^(t)Bu) and1,3-di-mesityl-butyl-imidazolin-2-ylidene (IMes) (Arduengo et al., J.Am. Chem. Soc. 1994, 116, 6641; Arduengo et al., J. Am. Chem. Soc. 1992,114, 5530), is drastically different. While IMes is also a highlyeffective catalyst for umpolung condensation of HMF to DHMF (5 mol %NHC, 93% DHMF by NMR), the more nucleophilic (I^(t)Bu) is completelyineffective. When HMF is mixed with a stoichiometric amount of NHC (TPT,IMes, or I^(t)Bu) at RT, HMF and NHC were completely consumed withoutproducing DHMF, presumably due to the formation of the correspondingadduct. The remarkable activity and efficiency of TPT in this carbenecatalysis is presumably related to the fact that TPT is both a goodnucleophile and leaving group, the latter of which is essential forclosing the catalytic cycle (c.f., FIG. 3).

By the same analogy, the ineffectiveness of I^(t)Bu can be attributed toits strong binding to HMF and being too poor a leaving group to closethe cycle. Overall, these results obtained from using the authentic,discrete NHC catalysts as well as the already established reactivity andfundamental steps of such NHCs towards aldehydes (i.e., benzoinreaction) further support the overall umpolung self-condensation of HMFto DHMF mechanism depicted in FIG. 3.

Accordingly, through organocatalysis by the catalytic acetate-based IL[EMIM]OAc, the chloride-based IL [EMIM]Cl in combination with theorganic base DBU, or the discrete NHC catalysts TPT and IMes, we havedeveloped a rapid, highly selective and high-yield upgrading of the keybiorefining intermediate HMF into DHMF, a potential high-valuebiorefinery product as an intermediate to kerosene/jet fuel. Thereaction time for this HMF upgrading process is within 1 hour underindustrially preferred conditions (i.e., ambient atmosphere, or 60-80°C.), and the DHMF selectivity is typically near quantitative and yieldsare up to 98% (HPLC or NMR) or 87% (unoptimized, isolated yield).

This work has also yielded the carbene catalysis mechanism for thisupgrading transformation by the catalytic IL, which has been supportedby four lines of evidence presented herein, including the directidentification of the resting intermediate. The technologicalsignificance of this work is that, while direct aldol condensation ofHMF for its upgrading is not possible (Huber, Chheda, Barrett, andDumesic, Science 2005, 308, 1446), the direct umpolung self-condensationof HMF for its upgrading into DHMF is highly facile, which is madepossible by organocatalysis. Additionally, as many efficient catalystsystems have been developed for conversion of plant biomass resources(glucose or cellulose) into HMF (see, for example, Zhang et al., Energy& Fuels 2010, 24, 2410), it is now possible to convert such nonfoodbiomass directly into DHMF via a two-step process. Indeed, our resultsshow the feasibility of transforming glucose directly into DHMF in astep-wise fashion, with the first step converting glucose into HMF bymetal catalysis, followed by extraction of HMF and subsequent carbenecatalysis.

Coupling Reactions and Product Analysis.

Typical Procedure for Studying HMF Degradation in [EMIM]OAc and theCorresponding Results.

HMF (0.10 g, 0.79 mmol) was mixed with [EMIM]OAc (0.14 g, equimolar toHMF) in a 5 mL vial. The vial was sealed and heated at 80° C. for aperiod of time in a temperature-controlled orbit shaker (300 RPM). Thereaction was quenched with ice-water and diluted with a known amount ofdeionized water. HMF was quantified with calibration curves generatedfrom the commercially available standard in water (Liu et al., Appl.Catal. A: Gen. 2012, 435/436, 78). A typical HPLC chromatogram of thereaction product is shown in FIG. 1. The results of HMF degradation in[EMIM]OAc monitored by HPLC are summarized in Table 1-1 and FIG. 7,which showed that [EMIM]OAc rapidly degrades HMF at 80° C.; forinstance, HMF degraded by 81.7 and 94.2 mol % after only 10 and 60 min,respectively.

TABLE 1-1 Data profiles (by HPLC) for HMF degradation in [EMIM]OAc.temperature time HMF degradation (° C.) (minutes) (mol %) 50 10 53.1 2055.2 30 62.1 50 68.7 60 69.7 80 10 81.7 20 88.5 30 89.9 60 94.2

For investigation of the HMF degradation kinetics in [EMIM]OAc, HMF(40.0 mg, 0.32 mmol) and hexamethylbenzene (2.0 mg, 0.012 mmol) werefully dissolved in 0.5 mL DMSO-d₆, followed by addition of [EMIM]OAc (1equiv relative to HMF) in 0.5 mL DMSO-d₆. The mixture was transferredinto a J. Young-type NMR tube and sealed with the Teflon valve. Themixture was heated to 80° C. on an NMR spectrometer and the reaction wasfollowed by taking ¹H NMR spectra of the reaction mixture atpredetermined time intervals. The results of HMF degradation in[EMIM]OAc monitored by NMR are summarized in FIG. 8 (profiles of HMFdegradation as a function of time) and FIG. 9 (the first-order plot ofHMF degradation for the initial time period).

Isolation and Characterization of DHMF Produced from HMF Degradation in[EMIM]OAc.

As FIG. 1 shows, the HPLC chromatogram of the reaction mixture from theincomplete HMF degradation in [EMIM]OAc exhibited a peak at 3.72 minutesfor the unreacted HMF, plus a large peak at 5.15 minutes for a newcompound formed during HMF degradation in [EMIM]OAc. To separate the newcompound from the reaction mixture after the reaction at 80° C. for 30minute, 1 mL water was added to fully dissolve the mixture, after which2 mL ethyl acetate (EtOAc) was added for extraction. The upper layer(EtOAc phase) was collected and the extraction was repeated four times.The new compound was obtained as a light yellow powder (50% isolatedyield based on HMF) after purification by the silica gel columnchromatography (eluent: EtOAc/hexane/methanol=8/2/1) and vacuum drying.

The degradation product (new compound) was identified as5,5′-di(hydroxymethyl)furoin (DHMF), as clearly shown by its ¹H and ¹³CNMR spectra (FIG. 10). ¹H NMR (CD₃OD): δ 7.39 (d, J_(H-H)=3.6 Hz, 1H,furan ring proton), 6.52 (d, J_(H-H)=3.6 Hz, 1H, furan ring proton),6.40 (d, J_(H-H)=3.3 Hz, 1H, furan ring proton), 6.30 (d, J_(H-H)=3.3Hz, 1H, furan ring proton), 5.87 (s, 1H, CHOH), 4.60 (s, 2H, CH₂OH),4.49 (s, 2H, CH₂OH). ¹³C NMR (CD₃OD): δ 187 (C═O), 163, 158, 154, 152,123, 112, 111, 110 (a total of 8 resonances for the furan ring carbons),71.7 (CHOH), 58.4 (CH₂OH), 58.2 (CH₂OH). M.p.=124-125° C.; HRMScalculated for C₁₂H₁₁O₆ [M−H]⁻: 251.0556. found: 251.0561.

The DHMF purified by the silica gel column chromatography wasrecrystallized by slow diffusion of hexanes into a methanol solution ofDHMF at room temperature over 7 d, affording colorless single crystalssuitable for X-ray diffraction analysis. Single crystals were quicklycovered with a layer of Paratone-N oil (Exxon, dried and degassed at120° C./10⁻⁶ Torr for 24 hours) after decanting the mother liquor. Acrystal was then mounted onto a thin glass fiber and transferred intothe cold nitrogen stream of a Bruker SMART CCD diffractometer. Thestructure was solved by direct methods and refined using the BrukerSHELXTL program library (SHELXTL, Version 6.12; Bruker Analytical X-raySolutions: Madison, Wis., 2001).

The structure was refined by full-matrix least-squares on F² for allreflections. All non-hydrogen atoms were refined with anisotropicdisplacement parameters, whereas hydrogen atoms were included in thestructure factor calculations at idealized positions. The solvedstructure showed two independent molecules with minor structuraldifferences in the unit cell (FIG. 2). Selected crystallographic datafor DHMF: C₂₄H₂₄O₁₂, Orthorhombic, space group Pna2₁, a=23.5497(17) Å,b=5.9975(4) Å, c=15.8768(10) Å, α=90°, β=90°, γ=90°, V=2242.4(3) Å³,Z=4, D_(calcd)=1.494 Mg/m³, GOF=1.040, R1=0.0524 [I>2σ(I)], wR2=0.1309.CCDC-887451 contains the supplementary crystallographic data for thispaper. These data can be obtained free of charge from The CambridgeCrystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.

The identification as well as spectroscopic and structuralcharacterizations of the HMF degradation product (DHMF) allowed formonitoring of DHMF formation and HMF degradation simultaneously by NMR(DMSO-d₆, 80° C., hexamethylbenzene as the internal standard). Theresults were summarized in Table 1-2, FIG. 8, and FIG. 11, showing thata high yield of 72.4% was achieved at 86.1% HMF conversion (degradation)after 25 minutes.

TABLE 1-2 Data (by NMR) for HMF degradation and DHMF yield in [EMIM]OAcat 80° C. time HMF degradation DHMF yield (min) (mol %) (mol %) 0 17.1 02 47.1 6.3 5 56.8 31.3 10 74.2 54.3 15 81.9 58.5 20 84.0 66.9 25 86.172.4 30 86.8 71.0 45 88.5 71.0 60 89.6 67.6

Identification of Intermediate II from the Reaction of HMF with[EMIM]OAc.

The 1:1 reaction of HMF with [EMIM]OAc at RT was monitored by NMR(DMSO-d₆) in a J. Young-type NMR tube using hexamethylbenzene as theinternal standard. This study showed that 17% HMF was consumedimmediately upon mixing HMF with [EMIM]OAc at RT, which approximatelycorresponds to the amount of the NHC catalyst accessible in [EMIM]OAc atthis temperature for its reaction with HMF to form intermediate II. Thisintermediate is not converted into DHMF at RT, even after 24 hours, andthe ¹H NMR remained the same from the beginning of the reaction up to 24hours at RT.

To aid analysis of the spectra of the in situ reactions, the chemicalshifts of the four species involved in the reaction of HMF with[EMIM]OAc were summarized as follows. All chemical shifts were reportedin DMSO-d₆, and the NMR solvent residual signal was referenced at 2.54ppm (not 2.50 ppm), based on the chemical shift of the hexamethylbenzeneinternal standard set at 2.15 ppm.

¹H NMR for HMF (known compound): δ 9.56 (s, 1H, CHO), 7.51, 6.59 (d, 2H,furan ring H), 4.54 (s, 2H, CH₂OH).

¹H NMR for [EMIM]OAc (known compound): δ 9.60 (s, 1H, NCHN), 7.84, 7.76(d, 2H, imidazolium ring H), 4.24 (q, 2H, NCH₂CH₃), 3.89 (s, 3H, NCH₃),1.65 (s, 3H, OAc), 1.44 (t, 3H, NCH₂CH₃).

¹H NMR for DHMF (new compound, see FIG. 10 in methanol-d₄ and FIG. 12 inDMSO-d₆): δ 7.54, 6.54, 6.38, 6.25 (d, 4H, furan ring H), 5.78 (s, 1H,CHOH), 4.50 (s, 2H, CH₂OH), 4.35 (s, 2H, CH₂OH).

¹H NMR for Intermediate II (new compound, see FIGS. 4 and 5): δ 7.98 (d,J_(H-H)=2.1 Hz, imidazol ring H), 7.93 (d, J_(H-H)=1.8 Hz, 1H, imidazolring proton), 6.74 (s, 1H, CH—OH), 6.38 (d, J_(H-H)=3.3, 1H, furan ringH), 6.24 (d, J_(H-H)=3.0 Hz, 1H, furan ring H), 4.41 (m, 2H, NCH₂CH₃),4.36 (s, 2H, CH₂OH), 3.96 (s, 3H, NCH₃), 1.64 (s, 3H, OAc), 1.31 (t,J_(H-H)=7.2 Hz, 3H, NCH₂CH₃). ¹³C NMR: δ 175 (C═O), 158 (NCN), 151, 146,109, 108 (4 resonances for the furan ring), 125, 122 (2 resonances forthe imidazol ring), 60.4 (CH—OH), 56.3 (CH₂OH), 44.2 (NCH₂CH₃), 36.2(NCH₃), 26.5 (O═C—CH₃), 16.3 (NCH₂CH₃).

Solvent-Free Umpolung Procedures for Coupling of Furaldehydes.

Umpolung reactions catalyzed by TPT were carried out under solvent-free(neat) conditions. Furfural (2.5 g, 26 mmol) was added in a 20 mL vial,to which TPT (71 mg, 0.26 mmol, 1.0 mol % to furfural) was added. Theresulting mixture was stirred for 1 hour, after which the solidifiedproduct was crushed and washed with hexanes. Furoin (2.2 g, 89% yield)was obtained as yellow powder after filtration and vacuum drying. Usingthe same procedure, 5,5′-dimethylfuroin was synthesized from MF in 94%isolated yield.

For the synthesis of 5,5′-di(hydroxymethyl)furoin (DHMF), HMF (2.5 g, 20mmol) was premixed with TPT (55 mg, 0.20 mmol, 1.0 mol % relative toHMF) in a 20 mL vial. The vial was sealed and heated at 60° C. for 1hour by a temperature-controlled orbit shaker (300 rpm). After thereaction, the solidified product was crushed and washed with toluene toremove the residual TPT catalyst. DHMF (2.4 g, 95% yield) was obtainedas white powder after filtration and vacuum drying.

Stoichiometric Reaction of HMF and N-Heterocyclic Carbene (NHC).

HMF (20 mg, 0.16 mmol) was dissolved into 0.5 mL DMSO-d₆ and transferredinto a J. Young-type NMR tube, to which a stoichiometric amount of IMes(48 mg, 0.16 mmol) in 0.5 mL DMSO-d₆ was added and fully mixed. After 30minutes at RT, the clean formation of the resulting enaminol, theBreslow intermediate involved in the benzoin reaction, was indicated by¹H NMR spectrum (FIG. 13). ¹H NMR (DMSO-d₆): δ 7.81 (s, 2H, imidazolering protons), 7.14 (s, 4H, benzene ring protons), 6.11 (d, J_(H-H)=3.0Hz, 1H, furan ring proton), 6.01 (d, J_(H-H)=3.3 Hz, 1H, furan ringproton), 4.31 (s, 2H, CH₂OH), 2.37 (s, 6H, p-CH₃), 2.08 (s, 12H, o-CH₃).

Typical Procedure for Studying Umpolung Condensation of HMF into DHMF byNHCs and the Corresponding Results.

In a typical procedure, HMF (115 mg, 0.91 mmol) was fully dissolved in 5mL THF, followed by addition of TPT (5 mol %) in 0.5 mL THF. Theresulting solution was stirred at room temperature, and aliquots weretaken from time to time and dried under vacuum for analysis by ¹H NMR inDMSO-d₆. To isolate DHMF from the HMF self-condensation catalyzed byTPT, the reaction mixture was stirred at room temperature for 24 hoursand then concentrated, followed by addition of toluene to precipitatethe product DHMF. DHMF (99 mg, 86% yield) was obtained as white solidafter filtration and vacuum drying. ¹H NMR in DMSO-d₆ of the product(FIG. 12) confirmed the clean formation of DHMF. The same reaction wasrepeated at 60° C. for 1 hour, affording DHMF in 87% isolated yield.

Table 1-3 summarizes selected results of the DHMF yield under variousconditions achieved by three NHC catalysts, TPT, I^(t)Bu, and IMes. Themost efficient catalyst in this series is TPT, which converted HMF toDHMF in 98% yield (by NMR, or 86% isolated yield) with a low catalystloading of 5 mol % at RT after 24 hours. The rate of HMF condensationcan be greatly enhanced when carrying out the reaction at 60° C., whichachieved 93.6% DHMF yield after 1 hour, compared to 37.5 DHMF yield atRT after 3 hours. In comparison, IMes is somewhat less effective thanTPT, but I^(t)Bu is completely ineffective. However, when astoichiometric amount of NHC (relative to HMF) was used at RT, in allcases HMF was completely consumed without forming DHMF.

TABLE 1-3 Results of HMF self-condensation to DHMF catalyzed by NHCs.DHMF yield DHMF yield NHC loading temperature time (NMR) (isolated) NHC(mol %) (° C.) (h) (%) (%) I^(t)Bu 5 25 24 0 0 100 25 24 0 0 IMes 5 2524 92.9 n.d. 100 25 24 0 0 TPT 5 25 24 98.0 86.2 100 25 24 trace n.d. 560 1 93.6 87.1 Solvent: THF. n.d. = not determined.

While [EMIM]Cl itself is ineffective for this catalysis, the[EMIM]Cl+DBU (5 mol %) system, which generates the NHC catalyst in situ,is highly effective for HMF upgrading. The NHC catalyst loading isconveniently controlled by the amount of DBU added to the reactionmixture. Specifically, HMF was premixed with [EMIM]Cl (1 equiv) and DBU(5 mol %) and heated at 80° C. for 1 hour, DHMF was formed in 96.4%yield (by HPLC). Potential co-solvent effects were also examined,showing a minimal effect on the DHMF yield; thus, addition of the THFco-solvent gave a DHMF yield of 96.7%, while the yield was 93.8% whenemploying DMF as a co-solvent.

Example 2. Upgrading Biomass Furaldehydes to Value-Added Chemicals,Oxygenated Diesel, and Premium Alkane Fuels

Recognized as a key biorefining building block and the biomass platformchemical, 5-hydroxymethylfurfural (HMF) has been studied extensively aspart of major efforts in developing technologically and economicallyfeasible routes for converting nonfood lignocellulosic biomass intofeedstock chemicals, sustainable materials, and liquid fuels. Since theimportant discovery of the CrCl₂/ionic liquid (IL) catalyst system foreffective conversion of the cellulosic glucose to HMF (Zhao et al.,Science 2007, 316, 1597), a large number of other metal or non-metalcatalyst systems have been developed to promote effective conversion ofglucose or directly cellulose into HMF (for example, see Liu and Chen,Biomass & Bioenergy, 2013, 48, 181-190). In contrast, research on theupgrading of HMF or related furaldehydes into higher molecular-weightand energy-density kerosene (C₈ to C₁₆) or diesel (up to C₂₂)intermediates or fuels is scarce and thus much needed.

Considering the fact that HMF cannot undergo self-aldol condensation dueto lack of an α-hydrogen, Dumesic and co-workers utilized cross-aldolcondensation of HMF with enolizable organic compounds such as acetone inthe presence of an alkaline catalyst, followed bydehydration/hydrogenation processes, to upgrade HMF into C₉ to C₁₅liquid alkane fuels (Scheme 2-1, route A) (Huber et al., Science, 2005,308, 1446). Recently, Corma and co-workers developed hydroxyalkylationof 2-methylfuran to perform trimerization in the presence of an acidcatalyst, the product of which is subject to high-temperaturehydrodeoxygenation (HDO) to produce high-cetane number 6-alkylundecanes(Corma et al., Angew. Chem. Int Ed. 2011, 50, 2375). HMF can be used toreplace one of the 2-methylfuran molecules in the trimerization step(Scheme 2-1, route B). Most recently, Bell and co-workers reportedacid-catalyzed etherification and reductive etherification of HMF into5-(alkoxymethyl)furfurals and 2,5-bis(alkoxymethyl)furans as potentialoxygenated biodiesel candidates (Scheme 2-1, route C) (Balakrishnan etal., Green Chem. 2012, 14, 1626). This direct HMF etherification routeoffers an alternative for producing usable diesel-range fuels to theetherification of the chloride derivative of HMF,5-(chloromethyl)furfural, with alcohol (Mascal and Nikitin, Green Chem.2010, 12, 370).

Recent research on hydrodeoxygenation (HDO) has focused on thedevelopment of bifunctional catalysts for upgrading lignin-derivedpyrolysis oils (phenols, guiaiacols and syringols, etc.) intohydrocarbons. Water can be used as a suitable solvent for HDO, allowingfor spontaneous separation of hydrocarbons during the reaction.Supported catalysts such as Ni/HZSM-5, Pd/C+H₃PO₄ and Pd/C+HZSM-5 canachieve high to quantitative yield of cycloalkanes from phenols under 5MPa H₂ at 250° C. within 2 hours (Zhao and Lercher, Angew. Chem. Int Ed.2012, 51, 5935). However, for furan compounds derived from cellulosicbiomass, HDO products are complicated by furan-ring opening, carbonchain fragmentation, rearrangement, and cyclization, rendering a widedistribution of hydrocarbons.

Using conditions similar to those employed for the HDO of thelignin-derived pyrolysis oils, the HDO of furfural gave tetrahydropyranin 36% yield besides pentane. For the HDO of 5-methylfuran trimer(5,5-bisylvyl-2-pentanone) by Pt/C and Pt/TiO₂ under 5 MPa H₂ and 400°C., 96% oily products were classified as C₉ to C₁₆ hydrocarbons (linear,branched, monocyclic, and bicyclic). In a two-step HDO of furoinconsisting of hydrogenation by Pd/Al₂O₃ to render the substrate watersoluble and the subsequent HDO process with Pt/SiO₂—Al₂O₃, Dumesic etal. obtained a wide distribution of alkanes, with 34% C₁₀ selectivity(Science, 2005, 308, 1446). The HDO of the reductive Pinacol couplingproducts of furfural and 5-methylfurfural (MF) by Pt/C and solid acidTaOPO₄ afforded high yield of alkanes (Huang et al., RSC Advances, 2012,2, 11211). Alternatively, opening the furan rings first under mildconditions (which is applicable only to certain types of furan rings),followed by HDO, could potentially produce alkanes more selectively.

Direct coupling of two HMF molecules would provide a sulfur-free C₁₂jet/kerosene fuel intermediate, which could be catalytically reformedinto liquid fuels. Herein we report the selective and quantitativecoupling of HMF to 5,5′-di(hydroxymethyl)furoin (DHMF) undersolvent-free conditions using 1 mol % of an organic N-heterocycliccarbene (NHC) catalyst and subsequent transformations of DHMF intooxygenated diesel fuels through hydrogenation, etherification oresterification, as well as high quality kerosene/jet fuels through ahighly selective HDO process that produces nearly quantitative linearhydrocarbons (96% C₁₀₋₁₂ linear alkanes) in the organic phase (Scheme2-1, route D).

As discussed above in Examples 1 and 2, through the NHC-catalyzedumpolung benzoin condensation mechanism in the presence of a catalyticacetate IL, 1-ethyl-3-methylimidazolium acetate, or a discrete NHCcatalyst (5 mol %1,3,4-triphenyl-4,5-dihydro-1H-1,2,4-triazol-5-ylidene, TPT), at 60° C.in THF for 1 h, HMF can be selectively self-coupled into DHMF, apromising new C₁₂ kerosene/jet fuel intermediate (Liu et al., GreenChem. 2012, 14, 2738-2746). This coupling reaction is unique to theorganically catalyzed umpolung reaction, as other types of couplingreactions, such as reductive Pinacol coupling, did not work for HMF.

As described in this example, we found that this catalytic couplingreaction can be carried out in the absence of any solvent, even thoughboth HMF and the NHC catalyst are solids (Scheme 2-2). With a TPTloading of 1 mol %, quantitative HMF conversion was observed at 60° C.after 1 hour and DHMF was formed quantitatively (by NMR) with a highisolated yield of 95%. Using a lower catalyst loading of 0.5 mol %, anisolated yield of 87% can still be achieved. Likewise, furfural and5-methylfurfural (MF) can also be coupled using 1 mol % TPT, even atroom temperature, into 1,2-di(furan-2-yl)-2-hydroxyethanone (furoin) and5,5′-dimethylfuroin in 89% and 94% isolated yields, respectively.

Umpolung of aldehydes catalyzed by NHCs is proposed to proceed throughthe nucleophilic enaminol or the Breslow intermediate involved in thebenzoin reaction. Indeed, we observed the formation of such anintermediate through the stoichiometric reaction of HMF and 1,3-bis(2,4,6-trimethylphenyl)-1,3-dihydro-2H-imidazol-2-ylidene (IMes) inDMSO-d₆ at ambient temperature (FIG. 13). This enaminol is the acylanion equivalent, thus attacking the carbonyl group of a second HMFmolecule to form another tetrahedral intermediate. Collapse of thistetrahedral intermediate, via proton transfer and elimination of theNHC, produces DHMF and regenerates the NHC catalyst, thus closing thecatalytic cycle and leading to the catalytic formation of the couplingproduct DHMF (Scheme 2-2).

As the self-condensation products of the three furaldehydes are solids,three routes were investigated to convert them into liquids as potentialjet or diesel fuels. We first examined the hydrogenation route toconvert the furoins into their saturated derivatives using therecyclable Pd/C catalyst. Under modest hydrogenation conditions (2.7 MPaH₂ and 90° C.) in the presence of 10 mol % Pd/C, all three furoins weresuccessfully converted into liquids (Scheme 2-3).

The liquids were not simply fully hydrogenated products, but accompaniedwith some hydrogenolysis products, as suggested by the elemental resultsthat showed C and H contents were higher than the theoretical values ofthe fully hydrogenated products (Table 2-1). Heating values of thehydrogenated products from furoin and 5,5′-dimethylfuroin were measuredto be 32.7 and 33.3 MJ/kg, respectively, which are noticeably higherthan that for ethanol (28.6 MJ/kg), approaching to the value fordimethylfuran (33.7 MJ/kg). These results indicated the potential use offuroin and 5,5′-dimethylfuroin as oxygenated liquid fuels after simplehydrogenation.

TABLE 2-1 Results of elemental analysis of hydrogenated couplingproducts. After Hydrogenation Before Theoretical ExperimentalHydrogenation Value Value furoins C (%) H (%) C (%) H (%) C (%) H (%)furoin 62.5 4.2 59.4 8.9 65.6 11.0 5,5′-dimethyl- 65.4 5.4 62.6 9.6 67.110.7 furoin DHMF 57.1 4.8 55.0 8.4 60.5 10.1

Next, following the procedures established for etherification of HMFwith alcohols to form 5-(alkoxymethyl)furfurals (Balakrishnan et al.,Green Chem. 2012, 14, 1626) and acetylation of the hydrogenated acetalderived from furfural and glycerol, we investigated etherification andesterification routes to convert DHMF into its corresponding ether withethanol and ester with propionic anhydride. Indeed, HMF, employed as acontrol run, was quantitatively converted to 5-ethoxymethylfurfural byNMR [¹H NMR (CDCl₃): δ 9.64 (s, 1H, CHO), 7.24, 6.55 (d, 2H, furan ringH), 4.56 (s, 2H, CH₂OH), 3.62 (q, 2H, CH₂CH₃), 1.28 (t, 3H, CH₂CH₃)] inexcess of ethanol at 75° C. for 24 hours with solid acid catalyst DowexG-26 (H-form) resin. Under similar conditions, DHMF was alsoquantitatively converted to the corresponding liquid ether,5,5′-di(ethoxymethyl)furoin (DEMF), with the secondary alcohol remainingintact (further discussed below). On the other hand, esterification ofDHMF using excess propionic anhydride esterified all three hydroxylgroups, thus forming DHMF-tripropionic ester (Scheme 2-3). Hence, boththe etherification and esterification routes can serve as alternativestrategies for liquefying DHMF into diesel fuels.

The third route utilized the HDO process through metal-acid tandemcatalysis. The overall HDO process of DHMF to linear alkanes (Scheme2-1) can proceed through metal-catalyzed hydrogenation to give thesaturated polyol, acid-catalyzed ring-opening/hydrolysis of furan ringsin aqueous solution to yield a straight-chain polyol, and acid-catalyzeddehydration, followed by metal-catalyzed hydrogenation to afford thefinal saturated linear C₁₂ alkane, n-dodecane, ideally with minimumfragmentation, branching, or cyclization. This overall picture calls fora bifunctional catalyst with both metal and acid sites (e.g., noblemetal on acidic support, Pt/CsH₂PW₁₂O₄₀ (Alotaibi et al., Chem. Commun.2012, 48, 7194; Tian et al., Chem. Eng. Technol. 2011, 34, 482)) topromote this HDO process, comprisinghydrogenation-ring-opening/hydrolysis-dehydration-hydrogenation cascadereactions. This picture is consistent with our results obtained from theabove hydrogenation over Pd/C that produces the furan-containing polyolwithout ring-opening (vide supra) and the observation by Dumesic et al.that hydrogenation, but not ring-opening, of the furan ring was theprimary reaction for the furan-containing compounds when subjected toHDO conditions using metal-acid bifunctional catalysts.

To generate hydrocarbon premium liquid fuels by the HDO process, weinvestigated HDO of DHMF under moderate conditions (250-300° C. and 3.5MPa H₂ pressure) with a number of bifunctional catalyst systems. Furoinwas reported to be converted to alkanes by a two-step process, with thefirst step being hydrogenation to make it soluble in water, followed bysubsequent HDO to avoid choking problems. As DHMF is water soluble, itsHDO process can be carried out directly in water without priorhydrogenation.

After initial catalyst screening, we identified three bifunctionalcatalyst systems that worked well for DHMF conversion to alkanes: (1)acidic solution (H₃PO₄) and Pd/C; (2) heteropoly acid (CsH₂PW₁₂O₄₀)supported Pt; (3) acidic solid catalyst (TaOPO₄) and Pt/C. In all cases,DHMF was completely converted and no or a negligible amount of alkanesbelow C₁₀ were observed. For the Pd/C+H₃PO₄ system (Table 2-2), thealkane selectivity in the organic phase was 38%, consisting of 8.6% C₁₀,17.6% C₁₁ and 12.2% C₁₂ alkanes.

TABLE 2-2 Analytical results of liquid fuels in the organic phase afterHDO in water. Conditions Isolated liquid fuels Temp. H₂ Time C₁₀ C₁₁ C₁₂Alkanes Oxygenated C H O Catalysts (° C.) (psi) (h) (%) (%) (%) (%) (%)(%) (%) (%) Pd/C + H₃PO₄ 250 500 2 8.6 17.6 12.2 38.4 61.6 75.2 12.612.2 Pt/CsH₂PW₁₂O₄₀ 250 500 2 — 11.3 40.6 51.9 48.1 79.4 13.0 7.6Pt/CsH₂PW₁₂O₄₀ ^(a) 250 500 2 6.1 15.2 — 24.7 75.3 77.8 12.6 9.6Pt/CsH₂PW₁₂O₄₀ 300 500 2 4.3 16.8 18.6 39.7 60.3 76.2 12.8 11.0 Pt/C +TaOPO₄ 300 500 3 27.0  22.9 45.6 95.5 4.5 81.2 14.6 4.2 ^(a)Biphasesystem with hexane/water = 50/50 mL.

A relatively higher alkane selectivity (52%) was obtained byPt/CsH₂PW₁₂O₄₀, consisting of 11.3% C₁₁ and 40.6% C₁₂ alkanes (FIG. 14).We also compared the performance of two different heteropoly-acids(CsH₂PW₁₂O₄₀ and C_(S2.5)H_(0.5)PW₁₂O₄₀), revealing thatPt/C_(S2.5)H_(0.5)PW₁₂O₄₀ only converted DHMF to a trace amount ofalkanes. This result shows that the stronger polyacid CsH₂PW₁₂O₄₀ isneeded to promote the furan ring opening. Varying HDO conditions,including a biphase system of hexane/water and higher temperature at300° C. (Table 2-2), actually lowered the alkane selectivity to 24.7%and 39.7%, respectively. The isolated liquid fuels, after the HDOprocess, contain noticeably higher carbon ratios (75-80%) than those byhydrogenation (60-66%). Most excitingly, utilizing the [Pt/C+TaOPO₄]catalyst system (Table 2-2), the highest alkane selectivity of 96% wasachieved at 300° C. for 3 hours, producing 27.0% C₁₀ (n-decane), 22.9%C₁₁ (n-undecane) and 45.6% C₁₂ (n-dodecane), FIG. 15. It is remarkableto see the clean formation of three linear C₁₀₋₁₂ alkanes through thishighly effective HDO process.

When compared with current methods for upgrading biomass furan compoundsinto biofuels, the DHMF route reported herein possesses at least thefollowing four advantages: (1) DHMF is obtained from self-coupling ofHMF, without the need for cross condensation with other petrochemicals;(2) HMF self-coupling is catalyzed by the organic NHC catalyst, whichcan be carried out under solvent-free conditions (neat) at 60° C. and 1hour affording DHMF in near quantitative isolated yield; (3) owing toits solubility in water, the HDO of DHMF can be carried out directly inwater, allowing for spontaneous separation of hydrocarbons from theaqueous phase; and (4) DHMF hydrodeoxygenation achieves high conversionand near quantitative selectivity towards linear C₁₀-C₁₂ alkanes with anarrow distribution of alkanes.

Accordingly, a highly effective new strategy for upgrading biomassfuraldehydes to liquid fuels has been developed and has been describedherein. This strategy includes the organocatalytic self-condensation(umpolung) of biomass furaldehydes into C₁₀₋₁₂ furoin intermediates,followed by hydrogenation, etherification or esterification intooxygenated biodiesel, or hydrodeoxygenation by metal-acid tandemcatalysis into premium hydrocarbon fuels. The umpolung coupling step iscarried out under solvent-free conditions, catalyzed by the organic NHC,and quantitatively selective and 100% atom-economical, all pointing tothe hallmarks of an extremely green process. Liquefying the C₁₀₋₁₂furoin intermediates can be readily accomplished by hydrogenation,etherification or esterification, producing oxygenated liquid biodieselwith considerably higher heating values than that of bioethanol. Mostsignificantly, premium hydrocarbon fuels can be produced throughhydrodeoxygenation of the C₁₂ DHMF in water under moderate conditions(300° C., 3 h, 3.5 MPa H₂) with the bifunctional catalyst system(Pt/C+TaOPO₄), which yields high quality alkane fuels with 96%selectivity to linear C₁₀₋₁₂ alkanes, consisting of 27.0% n-decane),22.9% n-undecane, and 45.6% n-dodecane.

Experimental Details 1,2-Di(5-hydromethyltetrahydrofuran-2-yl)ethyleneglycol (DHM-THF-EG) from Hydrogenation of DHMF

DHMF (0.1 g, 0.4 mmol) was dissolved in 30 mL THF and transferred to aParr High-pressure reactor, of which loaded Pd/C (20 mol % Pd). Thesuspension was stirred under pressurized H₂ (400 Psi) and heated at 90°C. for 6 hours. The Pd/C catalyst was collected after filtration andrecycled after washing with diethyl ether and dried under vacuum. Thefiltrate was dried overnight by high vacuum at room temperature. Theobtained viscous colorless liquid was identified by ¹H and ¹³C NMR andHRMS as DHM-THF-EG. HRMS calculated for C₁₂H₂₃O₆ [M+H]⁺: 263.1495.found: 263.1489. The NMR spectra were complex due to the presence ofseveral stereoisomers, but the absence of peaks at 5˜6 ppm clearly showsthat all furan ring double bonds were hydrogenated. The carbonyl doublebond was also hydrogenated, indicated by ¹³C NMR (no C═O signal) andHPLC-MS (no detection of carbonyl species).

1,2-Di(5-methyl-2-furanyl)-Ethanedione (DMF-EDO) and1,2-Di(5-methyl-furan-2-yl)ethylene glycol (DMF-EG) from Hydrogenolysisof DHMF

DHMF hydrogenolysis was carried out in a benzene-water biphase system.DHMF (0.1 g, 0.4 mmol) was first dissolved in 15 mL distilled water andtransferred to a Parr High-pressure reactor, of which loaded Pd/C (2 mol% Pd), HI (6 mol equiv, 57% water solution) and 20 mL benzene. Themixture was stirred under pressurized H₂ (400 Psi) and heated at 90° C.for 1 hour. After the reaction, the benzene phase was collected,filtered and dried by Rotovap. The resulting orange solids wereidentified as DMF-EDO. ¹H NMR in CDCl₃: δ 7.51 (d, J_(H-H)=2.7 Hz, 2H,furan ring protons), 6.23 (d, J_(H-H)=2.7 Hz, 2H, furan ring protons),2.43 (s, 6H, methyl group). This compound can be further hydrogenatedinto liquid fuel DMF-EG using the conditions described for DHM-THF-EG.

Tetrahydrofurans and methyltetrahydrofurans can be prepare by employingthe corresponding substrates of Scheme 2-3 where R═H or Me. A variety ofother products can be prepared by carrying out the hydrogenationreaction on other substituted furans prepare by the umpolung coupling offuraldehydes of Formula X. Additionally, DHMF can be modified prior toor after hydrogenation or hydrogenolysis to provide compounds with avariety of different substituents, as defined for substituents above.Examples include preparing various halide, amine, and amide substitutedcompounds, for example, as illustrated below. Substituent conversionscan be carried out after hydrogenation or hydrogenolysis to provide avariety of new tetrahydrofuran compounds.

where R is substituent as defined herein, for example, alkyl,cycloalkyl, acyl, aryl (e.g., phenyl or naphthyl), benzyl, benzoyl, andthe like, each optionally substituted with one or more substituents.

Etherification and Esterification of DHMF.

For etherification with ethanol, DHMF (0.10 g, 0.40 mmol) was dissolvedin 2.0 g ethanol in a 5 mL vial. Dowex G-26 H-form resin (24 mg) wasadded and the vial was heated in a temperature-controlled orbit shaker(75° C., 300 rpm) for 24 hours. After the reaction, the supernatantliquid was decanted, dried by anhydrous MgSO₄ and removed by vacuum.5,5′-Di(ethoxymethyl)furoin (DEMF) was obtained as viscous liquid. ¹HNMR for DEMF (DMSO-d₆): δ 7.21, 6.41, 6.31, 6.26 (d, 4H, furan ring H),5.75 (s, 1H, CHOH), 4.61 (s, 2H, CH₂OH), 4.38 (s, 2H, CH₂OH), 3.69 (q,2H, CH₂CH₃), 3.48 (q, 2H, CH₂CH₃), 1.15-1.24 (m, 6H, CH₂CH₃). HRMScalculated for C₁₆H₂₁O₆ [M+H]⁺: 309.1338. found: 309.1333. Mono-, di-,and tri-ethers of DHMF, and/or mixtures thereof, can be prepared bycontrolling the amount of alcohols added.

For esterification, DHMF (0.10 g, 0.40 mmol) was mixed with propionicanhydride (0.26 g, 2.0 mmol) in a 5 mL vial and heated at 130° C. for 2hours in a temperature-controlled orbit shaker. After the reaction,excess propanoic anhydride was removed by treatment with a saturatedaqueous solution of NaHCO₃, and the DHMF-tripropionic ester was obtainedas viscous liquid after extraction with ethyl acetate, drying withanhydrous MgSO₄ and further solvent removal and drying. ¹H NMR for theDHMF-tripropionic ester (CDCl₃): δ 7.26, 6.54, 6.50, 6.41 (d, 4H, furanring H), 5.19 (s, 1H, CHOH), 5.11 (s, 2H, CH₂OH), 5.06 (s, 2H, CH₂OH),2.39 (m, 6H, CH₂CH₃), 1.14-1.25 (m, 9H, CH₂CH₃). HRMS calculated forC₁₂H₂₈NO₉ [M+NH₄]⁺: 438.1764. found: 438.1759. Mono, di, and tri-estersof DHMF, and mixtures thereof, can be prepared by controlling the amountof propionic anhydride added.

Hydrogenation of Furoins.

Furoin (2.20 g, 11.4 mmol) was dissolved in 100 mL THF or methanol andtransferred to a Parr pressure reactor, to which Pd/C (4.84 g, 10 mol %Pd to furoin) was added. The system was purged with Hz for 15 minutesand heated at 90° C. for 6 hours under 400 psi Hz. After the reaction,Pd/C was recycled by filtration, and the filtrate was dried undervacuum. The hydrogenated furoin was obtained as liquid and subjected toelemental analysis and heating value test. 5,5′-Dimethylfuroin and DHMFwere hydrogenated in a similar fashion. ¹H NMR spectrum shows that afterhydrogenation, the furan double bonds were fully hydrogenated. HRMScalculated for DHMF after hydrogenation, C₁₂H₂₃O₆ [M+H]⁺: 263.1495.found: 263.1489. See Table 2-1.

Hydrodeoxygenation of DHMF.

DHMF (500 mg, 1.98 mmol) was dissolved in 50 mL distilled water andtransferred to a Parr pressure reactor. To this reactor was added acatalyst, either Pd/C (0.25 g)+H₃PO₄ (0.175 mL, 0.5 wt %) orPt/CsH₂PW₁₂O₄₀ (0.25 g). For the HDO by the Pt/C+TaOPO₄ system, theloading of DHMF, Pt/C, and TaOPO₄ was 0.25 g, 0.125 g, and 0.25 g,respectively. The reactor was purged with Hz for 15 minutes and heatedat 250° C. for 2 hours under 500 psi H₂ (the Pt/C+TaOPO₄ system washeated at 300° C. for 3 hours under 500 psi Hz). After the reaction, theorganic phase was extracted with DCM and analyzed by GC. Alkaneselectivity was reported based on the percentage of peak areas measuredby GC-FID. The organic phase was further dried with anhydrous MgSO₄ andthe solvent was removed under vacuum. The remaining oily products weresubjected to elemental analysis. See Table 2-2.

While specific embodiments have been described above with reference tothe disclosed embodiments and examples, such embodiments are onlyillustrative and do not limit the scope of the invention. Changes andmodifications can be made in accordance with ordinary skill in the artwithout departing from the invention in its broader aspects as definedin the following claims.

All publications, patents, and patent documents are incorporated byreference herein, as though individually incorporated by reference. Nolimitations inconsistent with this disclosure are to be understoodtherefrom. The invention has been described with reference to variousspecific and preferred embodiments and techniques. However, it should beunderstood that many variations and modifications may be made whileremaining within the spirit and scope of the invention.

What is claimed is:
 1. A compound of Formula I:

wherein each R¹ is H, OH, halo, amine, alkylamino, dialkylamino, alkoxy,or acyloxy; and R² is OH, halo, amine, alkylamino, dialkylamino, alkoxy,or acyloxy; provided that at least one R¹ is not H.
 2. The compound ofclaim 1 wherein each R¹ is H, OH, halo, alkoxy, or acyloxy.
 3. Thecompound of claim 1 wherein R² is OH, halo, alkoxy, or acyloxy.
 4. Thecompound of claim 1 wherein each R¹ is H, OH, halo, alkoxy, or acyloxy;and R² is OH, halo, alkoxy, or acyloxy.
 5. The compound of claim 1wherein the compound is:

wherein each R is aryl or (C₁-C₁₂)alkyl.
 6. The compound of claim 1wherein the compound is:


7. The compound of claim 6 wherein the compound is DHMF:


8. A compound of Formula II:

wherein R¹ is H, OH, halo, amine, alkylamino, dialkylamino, alkoxy, oracyloxy; and R² is H, OH, halo, amine, alkylamino, dialkylamino, alkoxy,or acyloxy.
 9. The compound of claim 8 wherein R¹ is H, OH, halo,alkoxy, or acyloxy.
 10. The compound of claim 8 wherein R² is H, OH,halo, alkoxy, or acyloxy.
 11. The compound of claim 8 wherein R¹ is H,OH, halo, alkoxy, or acyloxy; and R² is H, OH, halo, alkoxy, or acyloxy.12. The compound of claim 8 wherein the compound is:

wherein each R is H, alkyl, or acyl.
 13. The compound of claim 8 whereinthe compound is:


14. A composition comprising a compound of claim 1 and one or more(C₈-C₂₂)alkanes.
 15. The composition of claim 14 wherein the(C₈-C₂₂)alkane is a (C₁₀-C₂₂)alkane.
 16. A composition comprising acompound of claim 7 and one or more (C₈-C₂₂)alkanes.
 17. The compositionof claim 16 wherein the (C₈-C₂₂)alkane is a (C₁₀-C₂₂)alkane.
 18. Amethod to prepare a C₁₂ alkane comprising contacting a compound ofFormula I:

wherein each R¹ is H, OH, alkoxy, or acyloxy; and R² is OH, alkoxy, oracyloxy; or a compound of Formula II:

wherein R¹ is H, OH, alkoxy, or acyloxy; and R² is H, OH, alkoxy, oracyloxy; with a bifunctional catalyst system that comprises palladium orplatinum metal and an acidic moiety under reaction conditions comprisingheat and H₂ pressure in water; thereby providing the C₁₂ alkane.
 19. Themethod of claim 18 wherein the compound of Formula I is5,5′-di(hydroxymethyl)furoin (DHMF), the bifunctional catalyst system isan acidic solid catalyst of the formula TaOPO₄ in combination with Pt/C,the temperature of the method is at least about 200° C., and thereaction is carried out under at least 2 MPa of hydrogen gas pressure,wherein C₁₂ alkane is produced.
 20. The method of claim 19 wherein thetemperature is at least about 300° C., and the hydrogen gas pressure isat least about 3.5 MPa.